Chronic kidney disease is associated with attenuated plasma metabolome response to oral glucose tolerance testing

Chronic kidney disease (CKD), a major public health problem, is associated with decreased anabolic response to insulin contributing to protein-energy wasting. Targeted metabolic profiling of the response to oral glucose tolerance testing (OGTT) may help identify metabolic pathways contributing to disruptions to insulin response in CKD. Using targeted metabolic profiling, we examined plasma metabolome in 41 moderate-to-severe non-diabetic CKD patients with estimated glomerular filtration rate (eGFR)<60ml/min per 1.73m2 (38.9+-12.7) and 20 healthy controls with normal eGFR (87.2+-17.7) before and after 2h of 75g oral glucose load. Compared to controls, CKD participants had higher lactate: pyruvate (L:P) ratio both at fasting and after oral glucose challenge. Total energy production estimated through GTP:GDP ratio was impaired during OGTT despite similar fasting GTP:GDP ratio. CKD group had sustained elevation of vitamin B family members, TCA cycle metabolites, and purine nucleotides in response to glucose challenge. Metabolic profiling in response to OGTT suggests a broad disruption of mitochondrial energy metabolism in CKD patients. These findings motivate further investigation into insulin sensitizers in patients with non-diabetic CKD and their impact on energy metabolism.

The Usefulness of Glycated Hemoglobin (HbA1c) in the Detection of Diabetes Mellitus

Background: Health conditions like Diabetes mellitus sometimes affects serious to health due to unavailability of accurate check. But with advancements of diagnostics test like glycated hemoglobin (HbA1c) can save many lives to detect Diabetes Mellitus. Objective: In this study our main goal is to evaluate the accuracy of glycated hemoglobin (HbA1c.) in the diagnosis of Diabetes Mellitus. Methods: The Tertiary Medical College, Bangladesh, outpatient department (OPD) conducted this cross-sectional study. Where information was gathered between January 2019 and January 2020. During the research, a total of 100 individuals were enrolled with contemporaneous FPG, OGTT and A1c findings and diabetes mellitus suspicion. Purposive sampling was used to acquire the samples according to the inclusion criteria. Results: Most of the patients in the research were aged 47 to 57. 30.8% of the population and the majority (60%) were male. 71% of diabetes patients were identified alone by A1c, followed by 66% by 2h OGTT, and 43% of diabetic patients were diagnosed solely by fasting plasma glucose (FPG). IFG was found in 58% of the patients, whereas OGTT found IGT in 20% of the patients, and A1c found IGT in 24% of the patients. The difference between A1c and OGTT in diagnosing glucose intolerance was statistically significant (P 0.0001). Conclusion: This study's findings support the use of HbA1c as a screening tool for type 2 diabetes. Increasing access to diabetes care in Bangladesh may be made easier by using the HbA1c test, which is less onerous for patients than either FPG or oral glucose tolerance testing.

Continuous Glucose Monitoring and HbA1c in Cystic Fibrosis: Clinical Correlations and Implications for CFRD Diagnosis

Context The clinical utility and implications of continuous glucose monitoring (CGM) in cystic fibrosis (CF) are unclear. Objective We examined the correlation between CGM measures and clinical outcomes in adults with CF, investigated the relationship between hemoglobin A1c (HbA1c) and CGM-derived average glucose (AG), and explored CGM measures that distinguish CFRD from normal and abnormal glucose tolerance. Design Prospective observational study. Participants 77 adults with CF. Main outcomes CGM and HbA1c measured at 2-3 time-points three months apart. Results Thirty-one of the 77 participants met American Diabetes Association-recommended diagnostic criteria for CFRD by oral glucose tolerance testing and/or HbA1c. In all participants, CGM measures of hyperglycemia and glycemic variability correlated with nutritional status and pulmonary function. HbA1c was correlated with AG (R 2=0.71, p=&lt;0.001), with no significant difference between this regression line and that previously established in type 1 and type 2 diabetes and healthy volunteers. Cutoffs of 17.5% time &gt;140 mg/dL and 3.4% time &gt;180 mg/dL had sensitivities of 87% and 90%, respectively, and specificities of 95%, for identifying CFRD. Area under the curve and percent of participants correctly classified with CFRD were higher for AG, standard deviation, % time &gt;140, &gt;180, and &gt;250 mg/dL than HbA1c. Conclusions CGM measures of hyperglycemia and glycemic variability are superior to HbA1c in distinguishing those with and without CFRD. CGM-derived AG is strongly correlated with HbA1c in adults with CF, with a similar relationship to other diabetes populations. Future studies are needed to investigate CGM as a diagnostic and screening tool for CFRD.

Full The Relationship between Continuous Glucose Monitoring and OGTT in Youth and Young Adults with Cystic Fibrosis

Context Early glucose abnormalities in people with CF (PwCF) are commonly detected by continuous glucose monitoring (CGM). Relationships between these CGM abnormalities and oral glucose tolerance testing (OGTT) in PwCF have not been fully characterized. Objective(s) 1) To determine the relationship between CGM and common OGTT-derived estimates of β-cell function, including C-peptide index and oral disposition index (oDI) and 2) to explore whether CGM can be used to screen for OGTT-defined prediabetes and cystic fibrosis related diabetes (CFRD). Study Design/Methods PwCF not on insulin and healthy controls ages 6-25 yrs were enrolled in a prospective study collecting OGTT and CGM. A subset underwent frequently-sampled OGTTs (fsOGTT) with 7-point glucose, insulin, and C-peptide measurements. Pearson’s correlation coefficient was used to test the association between select CGM and fsOGTT measures. ROC analysis was applied to CGM variables to determine the cutoff optimizing sensitivity and specificity for detecting prediabetes and CFRD. Results A total of 120 participants (controls=35, CF=85), including 69 with fsOGTTs, were included. CGM coefficient of variation correlated inversely with C-peptide index (Cpeptide30-Cpeptide0/Glucose30-Glucose0) (r=-0.45, p&lt;0.001) and oDIcpeptide (C-peptide index)(1/cpep0) (r=-0.48, p&lt;0.0001). In PwCF, CGM variables had ROC-AUCs ranging from 0.43-0.57 for prediabetes and 0.47-0.6 for CFRD. Conclusions Greater glycemic variability on CGM correlated with reduced β-cell function. However, CGM performed poorly at discriminating individuals with and without OGTT-defined CFRD and prediabetes. Prospective studies are now needed to determine how well the different tests predict clinically-relevant non-glycemic outcomes in PwCF.

Detection and Management of Early Glucose Abnormalities in Cystic Fibrosis

With advances in technology, it is now possible to detect the emergence of glucose abnormalities in cystic fibrosis with improved sensitivity, and from a very early age. These abnormalities are increasingly recognized as predictors of clinical decline, raising the possibility that early intervention may slow or prevent this deterioration. In this chapter, we will review the available literature on methods of detecting glucose abnormalities in cystic fibrosis (random and fasting glucose, HbA1c, oral glucose tolerance testing, and continuous glucose monitoring), and detail their advantages and possible limitations in the interpretation of glycemic data. We will also discuss treatment outcomes of early intervention, prior to the diagnosis of diabetes as currently defined.

Comparison of Pregnancy Outcomes Using Different Gestational Diabetes Diagnostic Criteria and Treatment Thresholds in Multiethnic Communities between Two Tertiary Centres in Australian and New Zealand: Do They Make a Difference?

Introduction: Australia, but not New Zealand (NZ), has adopted the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria to diagnose gestational diabetes (GDM). We compared pregnancy outcomes using these different diagnostic approaches. Method: Prospective data of women with GDM were collected from one NZ (NZ) and one Australian (Aus) hospital between 2007–2018. Aus screening criteria with 2-step risk-based 50 g Glucose Challenge Testing (GCT) followed by 75 g-oral glucose tolerance testing (OGTT): fasting ≥ 5.5, 2-h ≥ 8.0 mmol/L (ADIPS98) changed to a universal OGTT and fasting ≥5.1, 1-h ≥ 10, 2-h ≥ 8.5 mmol/L (IADPSG). NZ used GCT followed by OGTT with fasting ≥ 5.5, 2-h ≥ 9.0 mmol/L (NZSSD); in 2015 adopted a booking HbA1c (NZMOH). Primary outcome was a composite of macrosomia, perinatal death, preterm delivery, neonatal hypoglycaemia, and phototherapy. An Aus subset positive using NZSSD was also defined. RESULTS: The composite outcome odds ratio compared to IADPSG (1788 pregnancies) was higher for NZMOH (934 pregnancies) 2.227 (95%CI: 1.84–2.68), NZSSD (1344 pregnancies) 2.19 (1.83–2.61), and ADIPS98 (3452 pregnancies) 1.91 (1.66–2.20). Composite outcomes were similar between the Aus subset and NZ. Conclusions: The IADPSG diagnostic criteria were associated with the lowest rate of composite outcomes. Earlier NZ screening with HbA1c was not associated with a change in adverse pregnancy outcomes.