Hemoglobin A1c Trajectories in the First 18 Months After Diabetes Diagnosis in the SWEET Diabetes Registry

2021 ◽  
Author(s):  
Priya Prahalad ◽  
Anke Schwandt ◽  
Stephane Besancon ◽  
Meena Mohan ◽  
Barbora Obermannova ◽  
...  
Keyword(s):  
Hemoglobin A1c ◽  
Diabetes Diagnosis ◽  
Diabetes Registry

scholarly journals Financial Resources and Biomarkers of Aging in the National Health and Aging Trends Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 589-589
Author(s):  
Laura Samuel ◽  
Laken Roberts ◽  
Danielle Boyce ◽  
Melissa Hladek ◽  
Sarah LaFave ◽  
...  
Keyword(s):  
Hemoglobin A1c ◽  
Income Group ◽  
Cross Sectional Study ◽  
Financial Strain ◽  
Diabetes Diagnosis ◽  
Lower Income ◽  
Sampling Weights ◽  
Cross Sectional ◽  
Lower Income Group ◽  
Biomarkers Of Aging

Abstract Lower income and financial strain (i.e. difficulty making ends meet) are associated with worse aging biomarkers, but evidence among nationally representative samples is limited. This cross-sectional study tested whether income to poverty ratio (analyzed separately for those <500% vs. ≥500% poverty threshold) and financial strain are associated with biomarkers of aging among NHATS participants aged ≥65 years (n=4,648), adjusting for age, race/ethnicity, gender, smoking, BMI, and diabetes diagnosis for hemoglobin A1c. Sampling weights were applied. Among those with incomes <500% poverty, higher income was associated with lower hemoglobin A1c (b= -0.0196, p=0.007), CMV (b= -0.0689, p<0.001) and CRP (b= -0.0428, p=0.012). Among those with incomes ≥500%, higher income was associated with lower IL-6 (b= -0.0001, p=0.023) and lower CMV (b= -0.0001, p<0.001). Financial strain was not associated with biomarkers. Income is more strongly associated with biomarkers among the lower income group, calling for special attention to this vulnerable population.

scholarly journals Impact of rare and common genetic variants on diabetes diagnosis by hemoglobin A1c in multi-ancestry cohorts: The Trans-Omics for Precision Medicine Program

2019 ◽  
Author(s):  
Chloé Sarnowski ◽  
Aaron Leong ◽  
Laura M Raffield ◽  
Peitao Wu ◽  
Paul S de Vries ◽  
...  
Keyword(s):  
African Americans ◽  
Precision Medicine ◽  
Hemoglobin A1c ◽  
Sequence Data ◽  
African Ancestry ◽  
Low Frequency ◽  
Diabetes Diagnosis ◽  
Common Genetic Variants ◽  
Patients With Diabetes ◽  
The Uk

AbstractHemoglobin A1c (HbA1c) is widely used to diagnose diabetes and assess glycemic control in patients with diabetes. However, nonglycemic determinants, including genetic variation, may influence how accurately HbA1c reflects underlying glycemia. Analyzing the NHLBI Trans-Omics for Precision Medicine (TOPMed) sequence data in 10,338 individuals from five studies and four ancestries (6,158 Europeans, 3,123 African-Americans, 650 Hispanics and 407 East Asians), we confirmed five regions associated with HbA1c (GCK in Europeans and African-Americans, HK1 in Europeans and Hispanics, FN3K/FN3KRP in Europeans and G6PD in African-Americans and Hispanics) and discovered a new African-ancestry specific low-frequency variant (rs1039215 in HBG2/HBE1, minor allele frequency (MAF)=0.03). The most associated G6PD variant (p.Val98Met, rs1050828-T, MAF=12% in African-Americans, MAF=2% in Hispanics) lowered HbA1c (−0.88% in hemizygous males, −0.34% in heterozygous females) and explained 23% of HbA1c variance in African-Americans and 4% in Hispanics. Additionally, we identified a rare distinct G6PD coding variant (rs76723693 - p.Leu353Pro, MAF=0.5%; −0.98% in hemizygous males, −0.46% in heterozygous females) and detected significant association with HbA1c when aggregating rare missense variants in G6PD. We observed similar magnitude and direction of effects for rs1039215 (HBG2) and rs76723693 (G6PD) in the two largest TOPMed African-American cohorts and replicated the rs76723693 association in the UK Biobank African-ancestry participants. These variants in G6PD and HBG2 were monomorphic in the European and Asian samples. African or Hispanic ancestry individuals carrying G6PD variants may be underdiagnosed for diabetes when screened with HbA1c. Thus, assessment of these variants should be considered for incorporation into precision medicine approaches for diabetes diagnosis.

scholarly journals Cognitive Function following Diabetic Ketoacidosis in Children with New Onset or Previously Diagnosed Type 1 Diabetes

2020 ◽  
Author(s):  
Simona Ghetti ◽  
Nathan Kuppermann ◽  
Arleta Rewers ◽  
Sage R. Myers ◽  
Jeff E. Schunk ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Ketoacidosis ◽  
Hemoglobin A1c ◽  
Economic Status ◽  
Digit Span ◽  
Diabetes Diagnosis ◽  
Newly Diagnosed ◽  
Neurocognitive Assessment ◽  
New Onset

<b>Objective. </b>This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes, and whether the same is true in children who had been previously diagnosed after accounting for variations in glycemic control and other relevant factors.<b> Design. </b>We prospectively enrolled 758 children, 6- to 18-years-old, who presented with DKA in a randomized multi-site clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled. <b>Results. </b>Among all patients, moderate/severe DKA was associated with lower IQ (β=-.12, p<0.001), item-color recall (β=-0.08, p=0.010), and forward digit span (β=-0.06, p=0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β=-0.08, p=0.04). Among previously diagnosed patients, repeated DKA exposure and higher hemoglobin A1c were independently associated with lower IQ (β=-.10 and β=-0.09, respectively, ps <.01) and higher hemoglobin A1c was associated with lower item-color recall (β=-0.10, p=0.007), after accounting for hypoglycemia, diabetes duration, and socio-economic status.<b> Conclusion. </b>A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.<b> <br> </b>

scholarly journals Association of G6PD variants with hemoglobin A1c and impact on diabetes diagnosis in East Asian individuals

2020 ◽  
Vol 8 (1) ◽  
pp. e001091 ◽  
Author(s):  
Aaron Leong ◽  
Victor Jun Yu Lim ◽  
Chaolong Wang ◽  
Jin-Fang Chai ◽  
Rajkumar Dorajoo ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Minor Allele Frequency ◽  
Hemoglobin A1c ◽  
Fasting Glucose ◽  
African Ancestry ◽  
East Asian ◽  
Missense Variant ◽  
Minor Allele ◽  
Carrier Status ◽  
Diabetes Diagnosis

ObjectiveHemoglobin A1c (HbA1c) accuracy is important for diabetes diagnosis and estimation of overall glycemia. The G6PD-Asahi variant which causes glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to lower HbA1c independently of glycemia in African ancestry populations. As different G6PD variants occur in Asian ancestry, we sought to identify Asian-specific G6PD variants associated with HbA1c.Research design and methodsIn eight Asian population-based cohorts, we performed imputation on the X chromosome using the 1000 Genomes reference panel and tested for association with HbA1c (10 005 East Asians and 2051 South Asians). Results were meta-analyzed across studies. We compared the proportion of individuals classified as having diabetes/pre-diabetes by fasting glucose ≥100 mg/dL or HbA1c ≥5.7% units among carriers and non-carriers of HbA1c-associated variants.ResultsThe strongest association was a missense variant (G6PD-Canton, rs72554665, minor allele frequency=2.2%, effect in men=−0.76% unit, 95% CI −0.88 to −0.64, p=1.25×10−27, n=2844). Conditional analyses identified a secondary distinct signal, missense variant (G6PD-Kaiping, rs72554664, minor allele frequency=1.6%, effect in men=−1.12 % unit, 95% CI −1.32 to −0.92, p=3.12×10−15, pconditional_Canton=7.57×10−11). Adjusting for glucose did not attenuate their effects. The proportion of individuals with fasting glucose ≥100 mg/dL did not differ by carrier status of G6PD-Canton (p=0.21). Whereas the proportion of individuals with HbA1c ≥5.7% units was lower in carriers (5%) compared with non-carriers of G6PD-Canton (30%, p=0.03).ConclusionsWe identified two G6PD variants in East Asian men associated with non-glycemic lowering of HbA1c. Carriers of these variants are more likely to be underdiagnosed for diabetes or pre-diabetes than non-carriers if screened by HbA1c without confirmation by direct glucose measurements.

scholarly journals Cognitive Function following Diabetic Ketoacidosis in Children with New Onset or Previously Diagnosed Type 1 Diabetes

2020 ◽  
Author(s):  
Simona Ghetti ◽  
Nathan Kuppermann ◽  
Arleta Rewers ◽  
Sage R. Myers ◽  
Jeff E. Schunk ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Ketoacidosis ◽  
Hemoglobin A1c ◽  
Economic Status ◽  
Digit Span ◽  
Diabetes Diagnosis ◽  
Newly Diagnosed ◽  
Neurocognitive Assessment ◽  
New Onset

<b>Objective. </b>This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes, and whether the same is true in children who had been previously diagnosed after accounting for variations in glycemic control and other relevant factors.<b> Design. </b>We prospectively enrolled 758 children, 6- to 18-years-old, who presented with DKA in a randomized multi-site clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled. <b>Results. </b>Among all patients, moderate/severe DKA was associated with lower IQ (β=-.12, p<0.001), item-color recall (β=-0.08, p=0.010), and forward digit span (β=-0.06, p=0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β=-0.08, p=0.04). Among previously diagnosed patients, repeated DKA exposure and higher hemoglobin A1c were independently associated with lower IQ (β=-.10 and β=-0.09, respectively, ps <.01) and higher hemoglobin A1c was associated with lower item-color recall (β=-0.10, p=0.007), after accounting for hypoglycemia, diabetes duration, and socio-economic status.<b> Conclusion. </b>A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.<b> <br> </b>

scholarly journals Comparison of Demographic and Diagnostic Markers in New Onset Pediatric Type 1 and Type 2 Diabetes

2021 ◽  
Author(s):  
Teresa Nieto ◽  
Beatriz Castillo ◽  
Jacobo Nieto ◽  
Maria Jose Redondo
Keyword(s):  
Type 2 Diabetes ◽  
Ethnic Minority ◽  
Hemoglobin A1c ◽  
Multiple Logistic Regression Analysis ◽  
Islet Autoantibody ◽  
Diabetes Diagnosis ◽  
C Peptide ◽  
Racial Ethnic

Purpose Type 1 diabetes (T1D) is the most common type of diabetes in children, but the frequency of type 2 diabetes (T2D) is increasing rapidly. Classification of diabetes is based on a constellation of features that are typical of each type. We aimed to compare demographic, clinical and laboratory characteristics at diabetes diagnosis in pediatric T1D and T2D. Methods We studied children who attended a large academic hospital in Houston, Texas (USA) with a new diagnosis of T2D (n=753) or T1D (n=758). We compared age, sex, race/ethnicity, presence of obesity, glucose, hemoglobin A1c, islet autoantibody positivity, C-peptide, and presence of diabetic ketoacidosis (DKA) at diabetes diagnosis. Results At diagnosis of diabetes, children with T2D, compared with those with T1D, were older (13.6 vs 9.7% years old), more likely females (63.2% vs 47.8%), of racial/ethnic minority (91.1%% versus 42.3%) and obese (90.9% vs 19.4%), and were less likely to have DKA (7.8% vs 35.0%) and diabetes autoantibodies (5.5% vs 95.4%). Children with T2D also had significantly less marked elevation of glucose and hemoglobin A1c, and lower C-peptide levels (all comparisons, p<0.0001). In multiple logistic regression analysis, older age, racial/ethnic minority, obesity, higher C-peptide and negative islet autoantibodies were independently associated with T2D (all, p<0.05) while sex, glucose, hemoglobin A1c and DKA were not (model p<0.0001). Conclusions There are important demographic, clinical and laboratory differences between T1D and T2D in children with T1D. However, none of the characteristics was unique to either diabetes type, which poses challenges to diabetes classification at diagnosis.

scholarly journals A combined polygenic score of 21,293 rare and 22 common variants significantly improves diabetes diagnosis based on hemoglobin A1C levels

2021 ◽  
Author(s):  
Peter Dornbos ◽  
Ryan Koesterer ◽  
Andrew Ruttenburg ◽  
Joanne B Cole ◽  
Aaron Leong ◽  
...  
Keyword(s):  
Rare Variant ◽  
Genetic Variants ◽  
Hemoglobin A1c ◽  
Rare Variants ◽  
Treatment Strategies ◽  
Common Variant ◽  
Common Disease ◽  
Diabetes Diagnosis ◽  
Common Variants ◽  
Polygenic Scores

Polygenic scores (PS), constructed from the combined effects of many genetic variants, have been shown to predict risk or treatment strategies for certain common diseases. As most PS to date are based on common variants, the benefit of adding rare variation to PS remains largely unknown and methodically challenging. We developed and validated a novel method for constructing a rare variant PS and applied it to a previously identified clinical scenario, in which genetic variants modify the hemoglobin A1C (HbA1C) threshold recommended for type 2 diabetes (T2D) diagnosis. The resultant rare variant PS is highly polygenic (21,293 variants across 144 genes), depends on ultra-rare variants (72.7% of variants observed in <3 people), and identifies significantly more undiagnosed T2D cases than expected by chance (OR=2.71, p=1.51x10-6). A model combining the rare variant PS with a previously published common variant PS is expected to identify 4.9M misdiagnosed T2D cases in the USA, nearly 1.5-fold more than the common variant PS alone. These results provide a method for constructing complex phenotype PS from rare variants and suggest that rare variants will augment common variants in precision medicine approaches for common disease.

scholarly journals Sulfonylurea Treatment Before Genetic Testing in Neonatal Diabetes: Pros and Cons

2014 ◽  
Vol 99 (12) ◽  
pp. E2709-E2714 ◽  
Author(s):  
David Carmody ◽  
Charles D. Bell ◽  
Jessica L. Hwang ◽  
Jazzmyne T. Dickens ◽  
Daniela I. Sima ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Glycemic Control ◽  
Genetic Diagnosis ◽  
Neurodevelopmental Outcome ◽  
Neonatal Diabetes ◽  
Diabetes Diagnosis ◽  
Neurodevelopmental Outcomes ◽  
Diabetes Registry ◽  
Pros And Cons ◽  
The University

Context: Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental outcomes in children with KCNJ11 or ABCC8 mutations, the most common gene causes. Objective: Assess the risks and benefits of initiating sulfonylurea therapy before genetic testing results become available. Design, Setting, and Patients: Observational retrospective study of subjects with neonatal diabetes within the University of Chicago Monogenic Diabetes Registry. Main Outcome Measures: Response to sulfonylurea (determined by whether insulin could be discontinued) and treatment side effects in those treated empirically. Results: A total of 154 subjects were diagnosed with diabetes before 6 months of age. A genetic diagnosis had been determined in 118 (77%), with 73 (47%) having a mutation in KCNJ11 or ABCC8. The median time from clinical diagnosis to genetic diagnosis was 10.4 weeks (range, 1.6 to 58.2 wk). In nine probands, an empiric sulfonylurea trial was initiated within 28 days of diabetes diagnosis. A genetic cause was subsequently found in eight cases, and insulin was discontinued within 14 days of sulfonylurea initiation in all of these cases. Conclusions: Sulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis.

Sign in / Sign up

Export Citation Format

Share Document