The development and utility of a novel scale that quantifies the glycemic progression toward type 1 diabetes over 6 months.
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ABSTRACT: Objective
We developed a scale to serve as a potential end point for 6-month glycemic progression (PS6M) toward type 1 diabetes (T1D) in autoantibody-positive relatives of individuals with T1D.Research design and methods
The PS6M was developed from Diabetes Prevention Trial-Type 1 (DPT-1) data and tested in the TrialNet Pathway to Prevention Study (PTP). It is the difference between 6-month glucose sum values (30-120 min oral glucose tolerance test values) and values predicted for nonprogressors.Results
The PS6M predicted T1D in the PTP (P < 0.001). The area under the receiver operating chacteristic curve was greater (P < 0.001) for the PS6M than for the baseline-to-6-month difference. PS6M values were higher in those with two or more autoantibodies, 30-0 min C-peptide values <2.00 ng/mL, or DPT-1 Risk Scores >7.00 (P < 0.001 for all).Conclusions
The PS6M is an indicator of short-term glycemic progression to T1D that could be a useful tool for assessing preventive treatments and biomarkers.
SUBMITTER: Sosenko JM
PROVIDER: S-EPMC4407750 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
Publications
The development and utility of a novel scale that quantifies the glycemic progression toward type 1 diabetes over 6 months.
Sosenko Jay M JM Skyler Jay S JS Beam Craig A CA Boulware David D Mahon Jeffrey L JL Krischer Jeffrey P JP Greenbaum Carla J CJ Rafkin Lisa E LE Matheson Della D Herold Kevan C KC Palmer Jerry P JP
Diabetes care 20150310 5
<h4>Objective</h4>We developed a scale to serve as a potential end point for 6-month glycemic progression (PS6M) toward type 1 diabetes (T1D) in autoantibody-positive relatives of individuals with T1D.<h4>Research design and methods</h4>The PS6M was developed from Diabetes Prevention Trial-Type 1 (DPT-1) data and tested in the TrialNet Pathway to Prevention Study (PTP). It is the difference between 6-month glucose sum values (30-120 min oral glucose tolerance test values) and values predicted fo ...[more]
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Project description:ObjectiveOn June 18 2018, Japan experienced the North Osaka Earthquake. The shaking intensity was recorded as level 6 of the Japan Meteorological Agency Seismic Intensity Scale. Despite the severe shaking, damages of lifelines and transportation networks were limited, and they were completely recovered within several days. We investigated whether the glycemic control in patients with diabetes was deteriorated over months after the earthquake.MethodsWe retrospectively analyzed diabetic outpatients attending the department of Metabolic Medicine, Osaka University Hospital, close to the epicenter of the earthquake, in 2018 (n = 1940), and those in 2017 (n = 1908) as a control. Whether glycated hemoglobin (HbA1c) levels were elevated after the earthquake, and whether the post-earthquake HbA1c elevation was more prevalent in areas with a higher seismic intensity were investigated using the mixed effects model.ResultsCompared to the same periods in 2017, mean HbA1c levels in 2018 were significantly higher 3-6 months after the earthquake (P < 0.05). The risk of HbA1c ≥ 7.0% was 1.6 (95% confidence interval 1.2-2.2) and 1.7 (1.2-2.4) times higher 3-4 and 5-6 months after the earthquake. Furthermore, the proportion of HbA1c deterioration after the earthquake was higher in areas with a higher seismic intensity (P for trend = 0.025).ConclusionGlycemic control was significantly deteriorated over months after the 2018 North Osaka Earthquake despite limited damage of lifelines and transportation networks. The deterioration was more prevalent in areas with a high seismic intensity.
| S-EPMC7790924 | biostudies-literature
Project description:BackgroundElectrochemiluminescence (ECL) assays have shown promise for enhancing the prediction of type 1 diabetes (T1D) with autoantibodies. We thus studied relatives of T1D patients to determine whether ECL assays can be used to refine risk assessments for T1D among individuals either positive for single GADA or single mIAA autoantibodies.Subjects and methodsTrialNet Pathway to Prevention (PTP) study participants with either GADA or mIAA single autoantibodies were tested for ECL positivity during their participation in the TrialNet PTP study. Those ECL positive (ECL+) were compared with those ECL negative (ECL-) for conversion to multiple autoantibodies, 6-month glycemic progression (PS6M), and the progression to T1D.ResultsThe progression to multiple autoantibodies was significantly higher for those GADA/ECL+ (n = 107) than those GADA/ECL- (n = 78) (P = 0.001) and for those mIAA/ECL+ (n = 24) than those mIAA/ECL- (n = 63) (P < 0.001). The hazard ratios with 95% confidence intervals were 3.42 (1.58-7.39; P < 0.01) for GADA and 8.15 (3.02-22.00; P < 0.001) for mIAA. GADA/ECL+ and mIAA/ECL+ participants had significantly higher PS6M values than their ECL- counterparts (P = 0.001 for GADA and P = 0.009 for mIAA). Of those GADA/ECL+, 14% progressed to T1D; of those mIAA/ECL+, 17% progressed to T1D. Only 1 individual (positive for GADA) of the 141 who was ECL- progressed to T1D (median follow-up: 5 years).ConclusionECL measurements appear to have utility for natural history studies and prevention trials of individuals with single autoantibodies. Those ECL+ are at appreciable risk for developing multiple autoantibodies and for glycemic progression toward T1D, whereas those ECL- are at very low risk.
| S-EPMC5359659 | biostudies-literature
Project description:ImportanceThe levels of glycemic control associated with the lowest risk of dementia in people with type 2 diabetes are unknown. This knowledge is critical to inform patient-centered glycemic target setting.ObjectiveTo examine the associations between cumulative exposure to various ranges of glycated hemoglobin (HbA1c) concentrations with dementia risk across sex and racial and ethnic groups and the association of current therapeutic glycemic targets with dementia risk.Design, setting, and participantsThis cohort study included members of the Kaiser Permanente Northern California integrated health care system with type 2 diabetes who were aged 50 years or older during the study period from January 1, 1996, to September 30, 2015. Individuals with fewer than 2 HbA1c measurements during the study period, prevalent dementia at baseline, or less than 3 years of follow-up were excluded. Data were analyzed from February 2020 to January 2023.ExposuresTime-updated cumulative exposure to HbA1c thresholds. At each HbA1c measurement, participants were categorized based on the percentage of their HbA1c measurements that fell into the following categories: less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, 9% to less than 10%, and 10% or more of total hemoglobin (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01).Main outcomes and measuresDementia diagnosis was identified using International Classification of Diseases, Ninth Revision codes from inpatient and outpatient encounters. Cox proportional hazards regression models estimated the association of time-varying cumulative glycemic exposure with dementia, adjusting for age, race and ethnicity, baseline health conditions, and number of HbA1c measurements.ResultsA total of 253 211 participants were included. The mean (SD) age of participants was 61.5 (9.4) years, and 53.1% were men. The mean (SD) duration of follow-up was 5.9 (4.5) years. Participants with more than 50% of HbA1c measurements at 9% to less than 10% or 10% or more had greater risk of dementia compared with those who had 50% or less of measurements in those categories (HbA1c 9% to <10%: adjusted hazard ratio [aHR], 1.31 [95% CI, 1.15-1.51]; HbA1c≥10%: aHR, 1.74 [95% CI, 1.62-1.86]). By contrast, participants with more than 50% of HbA1c concentrations less than 6%, 6% to less than 7%, or 7% to less than 8% had lower risk of dementia (HbA1c<6%: aHR, 0.92 [95% CI, 0.88-0.97]; HbA1c 6% to <7%: aHR, 0.79 [95% CI, 0.77-0.81]; HbA1c 7% to <8%: aHR, 0.93 [95% CI, 0.89-0.97]).Conclusions and relevanceIn this study dementia risk was greatest among adults with cumulative HbA1c concentrations of 9% or more. These results support currently recommended relaxed glycemic targets for older people with type 2 diabetes.
| S-EPMC10111232 | biostudies-literature
Project description:Previous research using latent class analysis (LCA) identified classes of people with type 2 diabetes and specific profiles of depression and anxiety. Since LCA-derived anxious depression strongly predicts cardiovascular outcomes and mortality but cannot be applied to individuals, we developed a validated combined depression-anxiety metric, the Diabetes Anxiety Depression Scale (DADS), for potential clinical application in people with type 2 diabetes.1,337 participants with type 2 diabetes from the observational community-based Fremantle Diabetes Study Phase II completed the Patient Health Questionnaire 9-item version (PHQ-9) to assess symptoms of depression, and the Generalised Anxiety Disorder Scale (GADS) to assess symptoms of anxiety. A single score was calculated by adding all the PHQ-9 items and the four GADS items used for the LCA. Cut-off scores were calculated with Receiver Operating Characteristic (ROC) area under the curve (AUC).The optimum cut-off scores in terms of sensitivity, specificity, positive and negative predictive value were 18 points for major anxious depression and 8 points for minor anxious depression. A score of 8-17 was associated with a significantly increased incidence of coronary heart disease, whereas a score 18-39 was associated with an increase in both coronary heart disease and cardiovascular mortality.The DADS has strong psychometric validity in the identification of mixed depression-anxiety in type 2 diabetes, and may contribute to cardiovascular risk prediction.
| S-EPMC5854400 | biostudies-literature
Project description:ObjectivesDecrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D.MethodsA total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes.ResultsCognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function.ConclusionsThe subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned.
| S-EPMC4856439 | biostudies-literature
Project description:ObjectiveThe Diabetes Control and Complications Trial (DCCT) demonstrated the beneficial effects of intensive versus conventional therapy on the development and progression of microvascular complications of type 1 diabetes. These beneficial effects were almost completely explained by the difference between groups in the levels of HbA1c, which in turn were associated with the risk of these complications. We assessed the association of glucose variability within and between quarterly 7-point glucose profiles with the development and progression of retinopathy, nephropathy, and cardiovascular autonomic neuropathy during the DCCT.Research design and methodsMeasures of variability included the within-day and updated mean (over time) of the SD, mean amplitude of glycemic excursions (MAGE), and M-value, and the longitudinal within-day, between-day, and total variances. Imputation methods filled in the 16.3% of expected glucose values that were missing.ResultsCox proportional hazards models assessed the association of each measure of glycemic variation, as a time-dependent covariate, with the risk of retinopathy and nephropathy, and a longitudinal logistic regression model did likewise for cardiovascular autonomic neuropathy. Adjusted for mean blood glucose, no measure of within-day variability was associated with any outcome. Only the longitudinal mean M-value (over time) was significantly associated with microalbuminuria when adjusted for the longitudinal mean blood glucose and corrected for multiple tests using the Holm procedure.ConclusionsOverall, within-day glycemic variability, as determined from quarterly glucose profiles, does not play an apparent role in the development of microvascular complications beyond the influence of the mean glucose.
| S-EPMC5439414 | biostudies-literature
Project description:ObjectiveType 2 diabetes mellitus (DM) accelerates brain aging and cognitive decline. Complex interactions between hyperglycemia, glycemic variability and brain aging remain unresolved. This study investigated the relationship between glycemic variability at multiple time scales, brain volumes and cognition in type 2 DM.Research design and methodsForty-three older adults with and 26 without type 2 DM completed 72-hour continuous glucose monitoring, cognitive tests and anatomical MRI. We described a new analysis of continuous glucose monitoring, termed Multi-Scale glycemic variability (Multi-Scale GV), to examine glycemic variability at multiple time scales. Specifically, Ensemble Empirical Mode Decomposition was used to identify five unique ultradian glycemic variability cycles (GVC1-5) that modulate serum glucose with periods ranging from 0.5-12 hrs.ResultsType 2 DM subjects demonstrated greater variability in GVC3-5 (period 2.0-12 hrs) than controls (P<0.0001), during the day as well as during the night. Multi-Scale GV was related to conventional markers of glycemic variability (e.g. standard deviation and mean glycemic excursions), but demonstrated greater sensitivity and specificity to conventional markers, and was associated with worse long-term glycemic control (e.g. fasting glucose and HbA1c). Across all subjects, those with greater glycemic variability within higher frequency cycles (GVC1-3; 0.5-2.0 hrs) had less gray matter within the limbic system and temporo-parietal lobes (e.g. cingulum, insular, hippocampus), and exhibited worse cognitive performance. Specifically within those with type 2 DM, greater glycemic variability in GVC2-3 was associated with worse learning and memory scores. Greater variability in GVC5 was associated with longer DM duration and more depression. These relationships were independent of HbA1c and hypoglycemic episodes.ConclusionsType 2 DM is associated with dysregulation of glycemic variability over multiple scales of time. These time-scale-dependent glycemic fluctuations might contribute to brain atrophy and cognitive outcomes within this vulnerable population.
| S-EPMC3901681 | biostudies-literature
Project description:Treatment guidelines for type 2 diabetes (T2D) recommend avoidance of hypoglycemia and less stringent glycemic control in older patients. We examined the relation of glycemic control to glucose-lowering medications use in a cohort of patients aged>80 years with a diagnosis of T2D and a hospital admission in the Capital Region of Denmark in 2012-2016. We extracted data on medication use, diagnoses, and biochemistry from the hospitals' records. We identified 5,172 T2D patients with high degree of co-morbidity and where 17% had an HbA1c in the range recommended for frail, comorbid, older patients with type 2 diabetes (58-75?mmol/mol (7.5-9%)). Half of the patients (n = 2,575) had an HbA1c <48?mmol/mol (<6.5%), and a majority of these (36% of all patients) did not meet the diagnostic criteria for T2D. Of patients treated with one or more glucose-lowering medications (n = 1,758), 20% had HbA1c-values <42?mmol/mol (<6%), and 1% had critically low Hba1c values <30?mmol/mol (<4.9%), In conclusion, among these hospitalized T2D patients, few had an HbA1c within the generally recommended glycemic targets. One third of patients did not meet the diagnostic criteria for T2D, and of the patients who were treated with glucose-lowering medications, one-fifth had HbA1c-values suggesting overtreatment.
| S-EPMC7057984 | biostudies-literature
Project description:BackgroundAround the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully.MethodsWe evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35-70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA.ResultsPostprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans.ConclusionsPinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups.
| S-EPMC3489574 | biostudies-literature
Project description:ContextDietary factors may trigger or exacerbate the autoimmune disease process.ObjectiveOur objective was to examine dietary glycemic index (GI) and glycemic load (GL) for association with islet autoimmunity (IA) development, and progression from IA to type 1 diabetes.DesignThe Diabetes Autoimmunity Study in the Young follows children at increased genetic type 1 diabetes risk. Diet is collected prospectively via a parent-reported food frequency questionnaire.SettingThis was an observational study of children in the Denver area.PatientsA total of 1776 Diabetes Autoimmunity Study in the Young children younger than 11.5 yr was included in the study.InterventionsThere were no interventions.Main outcome measuresIA, defined as the presence of autoantibodies to insulin, glutamic acid decarboxylase, or protein tyrosine phosphatase at two consecutive visits, or the presence of autoantibodies at one visit and diabetic on the next consecutive visit was determined. Type 1 diabetes was diagnosed by a physician. A total of 89 subjects developed IA, and 17 subsequently developed type 1 diabetes during follow-up. Our hypothesis was formulated after data collection.ResultsGI and GL were not associated with IA development. More rapid progression to type 1 diabetes in children with IA was associated with higher dietary GI (hazard ratio: 2.20; 95% confidence interval: 1.17-4.15) and marginally associated with GL (hazard ratio: 1.59; 95% confidence interval: 0.96-2.64) at the first IA-positive visit.ConclusionsHigher dietary GI and GL are not associated with IA development, but higher GI is associated with more rapid progression to type 1 diabetes in children with IA, perhaps due to increased demand on the beta-cell to release insulin. Further study is needed to confirm this finding and identify the underlying biological mechanism.
| S-EPMC2579644 | biostudies-literature