Diabetes Control And Complications Trial Research Articles

Seasonal variation of HbA1c levels in diabetic and non-diabetic patients

BackgroundHemoglobin A1c (HbA1c) serves as a pivotal marker for long-term glycemic control. The Diabetes Control and Complications Trial (DCCT) established its relevance, yet gaps exist in understanding potential seasonal variations in HbA1c levels among diabetic patients. The study highlights the need to explore potential seasonal variations in HbA1c levels and their impact on diabetic patients. Materials and methodsThis is an observational study conducted in a tertiary care hospital from January to December 2019, the study analyzed HbA1c levels in 8138 patients. Blood samples were collected using Potassium EDTA-containing vials and processed with an automated analyzer. Seasonal variations were explored using time series analysis. ResultsMean HbA1c levels peaked during the monsoon (June to September) and were lowest in autumn (October to November). Subgroup analysis revealed differences in patients with HbA1c values below and above 6.5 %. Those with controlled blood sugar showed higher levels in winter (December to February) and monsoon (June to September), while patients with HbA1c values ≥ 6.5 % exhibited significantly lower levels in monsoon (June to September) and autumn (October to November) compared to summer (March to May). ConclusionIn contrast to global trends, Indian patients demonstrated distinct seasonal variations in HbA1c levels. The highest levels during the monsoon (June to September) may be linked to reduced outdoor activity and dietary changes. The study emphasizes the need for tailored diabetes management considering seasonal influences. Further extensive, longitudinal studies across diverse Indian regions are recommended to comprehensively grasp the impact of seasonal changes on diabetes outcomes.

Associations of Kidney Tubular Biomarkers With Incident Macroalbuminuria and Sustained Low eGFR in DCCT/EDIC.

Tubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D). We performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning ∼30 years, with incident macroalbuminuria ("severely elevated albuminuria," urinary albumin excretion rate (AER) ≥300 mg/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR <60 mL/min/1.73 m2) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. Biomarkers included KIM-1 and sTNFR1 in serum/plasma, MCP-1 and EGF in urine, and a composite tubular secretion score reflecting secreted solute clearance. We assessed biomarkers using single values, as mean values from consecutive time points, and as change over consecutive time points, each as time-updated exposures. At baseline, mean diabetes duration was 5.9 years, with mean HbA1c 8.9%, eGFR 125 mL/min/1.73 m2, and AER 16 mg/day. There were 4.8 and 3.5 cases per 1,000 person-years of macroalbuminuria and low eGFR, respectively. Assessed according to single biomarker values, KIM-1 was associated with risk of subsequent macroalbuminuria and low eGFR (hazard ratio [HR] per 20% higher biomarker 1.11 [95% CI 1.06, 1.16] and 1.12 [1.04, 1.21], respectively) and sTNFR1 was associated with subsequent macroalbuminuria (1.14 [1.03, 1.25]). Mean KIM-1 and EGF-to-MCP-1 ratio were associated with subsequent low eGFR. In slope analyses, increases in KIM-1 and sTNFR1 were associated with subsequent macroalbuminuria (per 20% biomarker increase, HR 1.81 [1.40, 2.34] and 1.95 [1.18, 3.21]) and low eGFR (2.26 [1.65, 3.09] and 2.94 [1.39, 6.23]). Serial KIM-1 and sTNFR1 are associated with incident macroalbuminuria and sustained low eGFR in T1D.

Effectiveness of Insulin Pump Therapy Versus Multiple Daily Injections for Glycemic Control and Rate of Diabetic Ketoacidosis Among Children With Type 1 Diabetes Mellitus.

Background Advances in pump technology and the availability of insulin analogs, as well as the results of the Diabetes Control and Complications Trial (DCCT), which established the benefit of improved glycemic control, have all contributed to the increased use of insulin pump therapy in recent years, particularly in children. Purpose This research aims to compare the impact of insulin delivery method, i.e., continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) on glycemic control and the rate of diabetic ketoacidosis (DKA) among children with type 1 diabetes mellitus in Al Ahsa, Saudi Arabia. Methods A retrospective cohort study was carried out in a diabetic center in Al Ahsa, Saudi Arabia, over 24 months (2020-2022) among children with type I diabetes mellitus (age group 1-14 years). Results In total, 351patients with diabetes were induced, with 316 (90%) on MDIand 35 (10%) onCSII. After six months of diagnosis, precisely 38 (12%) ofpatients with diabetes on the MDIregimen experienced DKA, compared to 4 (11.4%) of those on the CSIIregimen, with no statistically significant difference (P=0.918). At six months and nine months of follow-up, the average hemoglobin A1c (HbA1c) was considerably higher in diabetic patients on MDI (8.9 ± 1.7% vs. 8.2 ± 1.5% and 9.1 ± 1.6% vs. 8.0 ± 1.3%, respectively, with a significant p-value ≤0.05). Conclusion In this study, we found that patients on the MDI regimen had considerably higher HbA1c levels than patients on the CSII regimen, but there was no statistically significant difference in DKA rates between them. This is a short-term follow-up study, and we recommend that patients be followed for a longer period of time for further accurate outcomes.

Methylglyoxal Adducts Are Prognostic Biomarkers for Diabetic Kidney Disease in Patients With Type 1 Diabetes.

Over 30% of patients with type 1 diabetes develop diabetic kidney disease (DKD), significantly increasing mortality risk. The Diabetes Control and Complications Trial (DCCT) and follow-up study Epidemiology of Diabetes Interventions and Complications (EDIC) established that glycemic control measured by HbA1c predicts DKD risk. However, the continued high incidence of DKD reinforces the urgent need for additional biomarkers to supplement HbA1c. Here, we assessed biomarkers induced by methylglyoxal (MG), a metabolic by-product that forms covalent adducts on DNA, RNA, and protein called MG-adducts. Urinary MG-adducts were measured from patients with type 1 diabetes enrolled in DCCT/EDIC who did (cases, n=90) or did not (controls, n=117) develop DKD. Univariate and multivariable analysis revealed that measurements of MG-adducts independently predict DKD, even before established DKD biomarkers such as glomerular filtration rate and albumin excretion rate. Elevated levels of MG-adducts bestowed the greatest risk of developing DKD in a multivariable model that included HbA1c and other clinical covariates. Our work establishes a novel class of biomarkers to predict DKD risk and suggests that inclusion of MG-adducts may be a valuable tool to improve existing predictors of complications like DKD prior to overt disease to aid in identifying at-risk individuals and personalized risk management.

Utility of the NIH Toolbox Cognition Battery in middle to older aged adults with longstanding type 1 diabetes: The DCCT/EDIC study

Objective: Adults with type 1 diabetes (T1D) face an increased risk for cognitive decline and dementia. Diabetes-related and vascular risk factors have been linked to cognitive decline using detailed neuropsychological testing; however, it is unclear if cognitive screening batteries can detect cognitive changes associated with aging in T1D. Method: 1,049 participants with T1D (median age 59 years; range 43–74) from the Diabetes Control and Complications Trial (DCCT), and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, completed the NIH Toolbox Cognition Battery (NIHTB-C) and Montreal Cognitive Assessment (MoCA). Neuropsychological assessments, depression, glycated hemoglobin levels (HbA1c), severe hypoglycemia, T1D complications, and vascular risk factors were assessed repeatedly over 32 years to determine associations with current NIHTB-C performance. Available cognitive data was clinically adjudicated to determine cognitive impairment status. Results: NIHTB-C scores had moderate associations (r = 0.36–0.53) with concurrently administered neuropsychological tests. In multivariate models, prior severe hypoglycemic episodes, depression symptoms, nephropathy, lower BMI, and higher HbA1c and LDL cholesterol were associated with poorer NIHTB-C Fluid Cognition Composite scores. The NIHTB-C adequately detected adjudicated cognitive impairment (Area Under the Curve = 0.86; optimal cut score ≤90). The MoCA performed similarly (Area Under the Curve = 0.83; optimal cut score ≤25). Conclusions: The NIHTB-C is sensitive to the cognitive effects of diabetes-related and vascular risk factors, correlated with neuropsychological testing, and accurately detects adjudicated cognitive impairment. These data support its use as a screening test in middle to older aged adults with T1D to determine if referral for detailed neuropsychological assessment is needed.

Narrative review of the role of technology in pediatric diabetes: from testing blood glucose to subcutaneous automated therapy and hope for cure.

Type 1 diabetes, the most common cause of diabetes in pediatrics, is defined by the hyperglycemia that results from the permanent autoimmune damage to the pancreas. The Diabetes Control and Complications Trial (DCCT) demonstrated that strict glycemic control targeting lower HbA1c goals can both delay the onset and progression of its complications that include diabetic neuropathy, nephropathy, retinopathy, and increased cardiovascular events. Our primary objective is to review the literature available regarding the technology applied for the treatment of diabetes, not only aiding patients' quality of life but addressing its effects on hypoglycemia and reduced risk of the long-term complications. It will synthesize the evolution of glucose monitoring devices; the development of insulin: from animal to recombinant engineering, smart insulin in the future; the development of algorithm-driven insulin delivery devices, the closed loop system/artificial pancreas; and the future utilization of technology to support islet cell transplant with the goal of a long-term cure. Emphasis will be made on what is known about the impact on its outcomes in children and adolescents. A literature search was conducted using PubMed for publications from 1985 to present. Keywords used: type 1 diabetes, children, adolescents, pediatrics, continuous glucose monitoring (CGM), insulin pumps. Referenced articles include other reviews, current care guidelines as supported by cross sectional studies, cohort studies and randomized clinical trials. Understanding the pathophysiology of type 1 diabetes has led to the design of technology that facilitates glucose monitoring and insulin administration in a personalized manner. The current technology has improved outcomes and quality of life by decreasing hypoglycemic events and decreasing risk of long-term metabolic complications. Barriers remain, for children and adults, often driven by patient's preference as well as their understanding of the limitations of what they are wearing. With the progressive evolution of this technology, it is now realistic to lower the burden of diabetes self-management while reducing hypoglycemia and risk of complications that otherwise impact daily life from academics, physical activity, career choices and even life expectancy.

Characterization of direct and/or indirect genetic associations for multiple traits in longitudinal studies of disease progression.

When quantitative longitudinal traits are risk factors for disease progression and subject to random biological variation, joint model analysis of time-to-event and longitudinal traits can effectively identify direct and/or indirect genetic association of single nucleotide polymorphisms (SNPs) with time-to-event. We present a joint model that integrates: (1) a multivariate linear mixed model describing trajectories of multiple longitudinal traits as a function of time, SNP effects, and subject-specific random effects and (2) a frailty Cox survival model that depends on SNPs, longitudinal trajectory effects, and subject-specific frailty accounting for dependence among multiple time-to-event traits. Motivated by complex genetic architecture of type 1 diabetes complications (T1DC) observed in the Diabetes Control and Complications Trial (DCCT), we implement a 2-stage approach to inference with bootstrap joint covariance estimation and develop a hypothesis testing procedure to classify direct and/or indirect SNP association with each time-to-event trait. By realistic simulation study, we show that joint modeling of 2 time-to-T1DC (retinopathy and nephropathy) and 2 longitudinal risk factors (HbA1c and systolic blood pressure) reduces estimation bias in genetic effects and improves classification accuracy of direct and/or indirect SNP associations, compared to methods that ignore within-subject risk factor variability and dependence among longitudinal and time-to-event traits. Through DCCT data analysis, we demonstrate feasibility for candidate SNP modeling and quantify effects of sample size and Winner's curse bias on classification for 2 SNPs identified as having indirect associations with time-to-T1DC traits. Joint analysis of multiple longitudinal and multiple time-to-event traits provides insight into complex traits architecture.

1336-P: Predicting the Progression of Stages of Neuropathy Using Routine Eye and Kidney Tests—An Application of Novel Statistical Methods in the Diabetes Control and Complications Trial (DCCT)

Despite recent advances, neuropathy screening is not consistently performed in clinical practice. We aimed to determine if neuropathy risk could be predicted using the trajectories of routinely-performed eye and kidney screening tests in T1D. We used 28-year data from the DCCT/EDIC study, available via the NIH public repository. We used the Early Treatment Diabetic Retinopathy Study Research (ETDRS) Group 23-point scale, albumin excretion rate (AER), and eGFR treated as longitudinal outcomes. Simultaneously, we represented neuropathy as a 3-state progressive multistate outcome using nerve conduction studies and the Michigan Neuropathy Screening Instrument (MNSI) for early-stage neuropathy and the occurrence of serious foot ulcer or amputation for late-stage neuropathy. To model these interrelated disease processes, we used and developed joint models with multistate submodels. Our “joint multistate model” accounted for interval censoring: due to the visit schedule, the exact time of transition to early-stage neuropathy was known only to occur in between consecutive visits. A Bayesian estimation procedure was used. We found that the risk of transition from no to early-stage neuropathy was affected by the current value of ETDRS, the current slope of ETDRS, and the current value of AER. For example, controlling for all covariates including eGFR, the there was a 23% higher rate of occurrence of this early-stage for a 3-step higher ETDRS scale. In the same model controlling for all covariates, progression from early-stage to late-stage neuropathy was affected mainly by AER (11% higher rate for a doubling of AER). Routinely-performed clinical eye and kidney test results can be leveraged to help identify the risk of neuropathy. Future work will develop dynamic predictions integrated into an electronic medical record. Disclosure L.Lovblom: None. L.Briollais: None. G.Tomlinson: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO).

Effect of Diabetes Supportive Group and Network (DINET) Programme on Quality of Life for Diabetes Patients

Gorontalo is ranked 7th in the number of people with diabetes from 35 provinces in Indonesia. One of the causes is the lack of self-care management which impacts the low quality of life of diabetes patients. Supportive group existence is needed as social support for diabetes patient, mainly in the community. This study's purpose is to analyze the effect of the DINET programme on the quality of life of diabetic people. The research method used a pre-experimental design through one group of pre and post-test analyses. The supportive group support provided activities involving diabetes patients, including health education, focus group discussion, physical exercise, and using chatbots and group chat as communication media for support group members. The sample used was 16 people through the purposive sampling method. The instrument for quality of life used is the Diabetes Instrument Quality of Life (DQOL) from the American Diabetes Control and Complications Trial (DCCT) Research Group. The study's results showed a significant difference in the quality of life of DM patients after the intervention with a p-value of 0.000 (α &lt; 0.05). The support group can be used as social support for diabetes patients to keep their discipline in self-care management to prevent dangerous complications.

Patterns of Regional Brain Atrophy and Brain Aging in Middle- and Older-Aged Adults With Type 1 Diabetes

Little is known about structural brain changes in type 1 diabetes (T1D) and whether there are early manifestations of a neurodegenerative condition like Alzheimer disease (AD) or evidence of premature brain aging. To evaluate neuroimaging markers of brain age and AD-like atrophy in participants with T1D in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, identify which brain regions are associated with the greatest changes in patients with T1D, and assess the association between cognition and brain aging indices. This cohort study leveraged data collected during the combined DCCT (randomized clinical trial, 1983-1993) and EDIC (observational study, 1994 to present) studies at 27 clinical centers in the US and Canada. A total of 416 eligible EDIC participants and 99 demographically similar adults without diabetes were enrolled in the magnetic resonance imaging (MRI) ancillary study, which reports cross-sectional data collected in 2018 to 2019 and relates it to factors measured longitudinally in DCCT/EDIC. Data analyses were performed between July 2020 and April 2022. T1D diagnosis. Psychomotor and mental efficiency were evaluated using verbal fluency, digit symbol substitution test, trail making part B, and the grooved pegboard. Immediate memory scores were derived from the logical memory subtest of the Wechsler memory scale and the Wechsler digit symbol substitution test. MRI and machine learning indices were calculated to predict brain age and quantify AD-like atrophy. This study included 416 EDIC participants with a median (range) age of 60 (44-74) years (87 of 416 [21%] were older than 65 years) and a median (range) diabetes duration of 37 (30-51) years. EDIC participants had consistently higher brain age values compared with controls without diabetes, indicative of approximately 6 additional years of brain aging (EDIC participants: β, 6.16; SE, 0.71; control participants: β, 1.04; SE, 0.04; P < .001). In contrast, AD regional atrophy was comparable between the 2 groups. Regions with atrophy in EDIC participants vs controls were observed mainly in the bilateral thalamus and putamen. Greater brain age was associated with lower psychomotor and mental efficiency among EDIC participants (β, -0.04; SE, 0.01; P < .001), but not among controls. The findings of this study suggest an increase in brain aging among individuals with T1D without any early signs of AD-related neurodegeneration. These increases were associated with reduced cognitive performance, but overall, the abnormal patterns seen in this sample were modest, even after a mean of 38 years with T1D.

Composite nerve conduction scores and signs for diagnosis and somatic staging of diabetic polyneuropathy: Mid North American ethnic cohort survey.

In the Diabetes Control and Complications Trial (DCCT), the minimal nerve conduction (NC) criterion for diabetic sensorimotor polyneuropathy (DSPN) was abnormality of NC in more than one peripheral nerve without specifying the attributes of NCs to be evaluated. In the present study, we assess individual and composite scores of NCs meeting the DCCT criterion and signs for improved diagnosis and assessment of DSPN severity. Evaluated were 13 attributes and 6 composite NC scores and signs and symptoms in 395 healthy subjects (HS) and 388 persons with diabetes (DM). Percent abnormality between subjects with DM and HS was remarkably different among individual attributes and the six composite NC scores. For diagnosis of DSPN using the DCCT criterion, assessment of conduction velocities (CVs) and distal latencies (DLs) provided sensitive diagnoses of DSPN. NC amplitudes provided stronger measures of severity. In studied cohorts, DSPN was staged: N0, no NC abnormality using NC score 2 (CVs and DLs), 60.0%; N1, NC abnormality only, 18.4%; N2, NC abnormality and signs of feet or legs, 16.3%; and N3, NC abnormality and signs of thighs, 5.3%. For sensitive and standard diagnosis of DSPN using the DCCT NC criterion, specifically defined composite scores of CVs and DLs, e.g., score 2, is recommended. A composite score of amplitudes, e.g., score 4, provides a stronger measure of neuropathy severity. Also, provided are HS reference values of evaluated attributes of NCs and estimates of staged severity of DSPN of mid North American DM cohorts.

1993 - The Diabetes Control and Complications Trial (DCCT)

1993 - The Diabetes Control and Complications Trial (DCCT)

Urinary Angiotensinogen in Patients With Type 1 Diabetes With Microalbuminuria: Gender Differences and Effect of Intensive Insulin Therapy

Angiotensinogen (AOG) is the precursor of peptides of the renin angiotensin system (RAS). Because insulin up-regulates transcriptional factors that normally repress kidney AOG synthesis, we evaluated urinary AOG (uAOG) in patients with type 1 diabetes (T1D) and microalbuminuria who are receiving either intensive or conventional insulin therapy. Urine samples from participants of the Diabetes Control and Complications Trial (DCCT) were used for the following: (i) uAOG/creatinine measurements in 103 patients with microalbuminuria and 103 patients with normoalbuminuria, matched for age, gender, disease duration, and allocation to insulin therapy; and (ii) uAOG/creatinine measurements from patients with microalbuminuria allocated to intensive insulin therapy (n= 58) or conventional insulin therapy (n= 41) after 3 years on each modality. uAOG was higher in patients who started with microalbuminuria than in those with normoalbuminuria (6.65 vs. 4.0 ng/mg creatinine, P< 0.01). uAOG was higher in females than in males with microalbuminuria (11.7 vs. 5.4 ng/mg creatinine, P= 0.015). uAOG was lower in patients with microalbuminuria allocated to intensive insulin therapy than in conventional insulin therapy (3.98 vs. 7.42 ng/mg creatinine, P< 0.01). These differences in uAOG were observed though albumin excretion rate (AER) was not significantly different. In patients with T1D and microalbuminuria, uAOG is increased and varies with gender and the type of insulin therapy independently of AER. This suggests that AOG production is increased in females and it is decreased by intensive insulin therapy. The reduction in uAOG with intensive insulin therapy, by kidney RAS downregulation, may contribute to the known renoprotective action associated with intensive insulin and improved glycemic control.

Type 1 diabetes mellitus and cardiovascular risk: A short review

The incidence of cardiovascular disease is substantially increased in patients with type 1 diabetes compared to the general population. Robust evidence from the randomized Diabetes Control and Complications Trial (DCCT) and the long-term epidemiologic surveillance of its participants suggest that tight glycemic control by means of intensive insulin treatment is efficacious both in primary and secondary prevention of cardiovascular disease. New antidiabetic agents with proven cardiorenal benefit in patients with type 2 diabetes, such as Glucagen-Like Polypeptide-1 Receptor Agonists (GLP-1RA) and Sodium-Glucose co-Transporter-2 Inhibitors (SGLT-2inh), have been tested as adjunctive to insulin treatment in a few clinical trials in patients with type 1 diabetes. Despite their favorable effect on risk factors for atherosclerotic disease, such as body weight and blood pressure, the lack of evidence for a direct effect on cardiovascular outcomes and an increased risk for serious adverse events, such as diabetic ketoacidosis, limit their use in patients with type 1 diabetes. New metrics of glycemia, alterations in diabetes classification and precision medicine may contribute in an individualized approach of cardiovascular risk prevention in patients with diabetes.

Plasma apoM Levels and Progression to Kidney Dysfunction in Patients With Type 1 Diabetes.

Apolipoprotein M (apoM), primarily carried by HDL, has been associated with several conditions, including cardiovascular disease and diabetic nephropathy. This study proposes to examine whether plasma apoM levels are associated with the development of diabetic kidney disease, assessed as progression to macroalbuminuria (MA) and chronic kidney disease (CKD). Plasma apoM was measured using an enzyme immunoassay in 386 subjects from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort at DCCT entry and closeout and the concentrations used to determine the association with risk of progression to kidney dysfunction from the time of measurement through 18 years of EDIC follow-up. apoM levels, at DCCT baseline, were higher in patients who developed CKD than in those who retained normal renal function. At DCCT closeout, participants who progressed to MA, CKD, or both MA and CKD also had significantly higher apoM levels than those who remained normal, and increased levels of apoM were associated with increased risk of progression to both MA (risk ratio [RR] 1.30 [95% CI 1.01, 1.66]) and CKD (RR 1.69 [95% CI 1.18, 2.44]). Our results strongly suggest that alterations in apoM and therefore in the composition and function of HDL in type 1 diabetes are present early in the disease process and are associated with the development of nephropathy.

Physical Function in Middle-aged and Older Adults With Type 1 Diabetes: Long-term Follow-up of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study.

To describe the prevalence and clinical correlates of functional limitations in middle-aged and older adults with long-standing type 1 diabetes. Functional limitations were assessed for 1,094 participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, a multicenter, longitudinal, observational follow-up of participants with type 1 diabetes randomly assigned to intensive or conventional diabetes therapy during the Diabetes Control and Complications Trial (DCCT). The primary outcome measure was a score <10 on the Short Physical Performance Battery (SPPB). The secondary outcome, self-reported functional limitation, was assessed by written questionnaire. Logistic regression models were used to assess associations of both outcomes with demographic and clinical factors (glycemic and nonglycemic factors, micro- and macrovascular complications, DCCT cohort, and treatment assignment). Participants were 53% male, with mean ± SD age 59.5 ± 6.8 years and diabetes duration 37.9 ± 4.9 years. The prevalence of SPPB score <10 was 21%. The prevalence of self-reported functional limitations was 48%. While DCCT treatment assignment was not associated with physical function outcomes measured ∼25 years after the end of the DCCT, the time-weighted mean DCCT/EDIC HbA1c was associated with both outcomes. Other clinical factors associated with both outcomes in multivariable analyses were BMI, general psychological distress, and cardiac autonomic neuropathy. Almost half of the middle-aged and older adults with long-standing type 1 diabetes reported functional limitations, which were associated with higher HbA1c and BMI, general psychological distress, and cardiac autonomic neuropathy. Future research is needed to determine whether these findings are generalizable.

353-OR: Determining the Sequence of Microvascular Complications: Results of Multistate Markov Modelling in the Diabetes Control and Complications Trial (DCCT)

Screening for neuropathy is complex and underperformed in practice. If neuropathy rarely occurs first, screening for it could be delayed until retinopathy or nephropathy are documented. To address this, we aimed to definitively determine the sequence of microvascular complications in the natural history of type 1 diabetes (T1D) . Using data available from the public NIDDK Repository (1983-2012) , independent of the DCCT/EDIC research group, we performed a multistate analysis using biostatistics techniques for complex trivariate processes of the 1441 participants with T1D. Retinopathy (‘Eye’, E) , nephropathy (‘Kidney’, K) , and neuropathy (‘Nerve’, N) were each screened repeatedly and defined by the early-stage phenotypes (Figure 1) . Our model accounted for intermittent ascertainment and differing screening schedules. At baseline, participants had mean age 27±7 years and duration 6±4 years. Markov model simulations started in the absence of complications (Ø) . Eye was the most common initial complication (49%) , followed by nerve (28%) , and kidney (22%) . Median time to first complication was 5.3 years. 4% had no complications through follow-up. While retinopathy is conclusively most common, the high frequency of other initial complications reinforces the current practice of unselected early screening for all three, including neuropathy. Disclosure L.Lovblom: None. L.Briollais: None. G.Tomlinson: None. B.A.Perkins: Advisory Panel; Abbott Diabetes, Insulet Corporation, Sanofi, Board Member; Novo Nordisk, Other Relationship; Abbott Diabetes, Insulet Corporation, Medtronic, Novo Nordisk, Research Support; BMO Bank of Montreal, Novo Nordisk. Funding The Canadian Institutes of Health Research and the public NIDDK Central Repository.

Risk factors for lower bone mineral density in older adults with type 1 diabetes: a cross-sectional study

Type 1 diabetes is associated with lower bone mineral density (BMD) and increased fracture risk, but little is known regarding the effects of diabetes-related factors on BMD. We assessed whether these factors are associated with lower hip BMD among older adults with type 1 diabetes. This cross-sectional study was embedded in a long-term observational study, the Epidemiology of Diabetes Interventions and Complications study (EDIC), a cohort of participants with type 1 diabetes, who were originally enrolled in the Diabetes Control and Complications Trial (DCCT), and were followed-up for more than 30 years at 27 sites in the USA and Canada. All active EDIC participants were eligible except if they were pregnant, weighed above the dual-energy x-ray absorptiometry (DXA) scanner limit, had an implanted neurostimulator, or were not willing to participate. The primary study outcome was total hip BMD. Hip, spine, and radius BMD and trabecular bone score (TBS) were measured with DXA at an annual EDIC visit (2017-19). Time-weighted mean HbA1c, kidney disease, and peripheral neuropathy were measured annually during EDIC, and retinopathy was measured every 4 years. Skin intrinsic fluorescence, a measure of advanced glycation end products (AGEs), and cardiac autonomic neuropathy were assessed once (2009-10) during EDIC. 1147 of the 1441 participants who were enrolled in the DCCT trial remained active EDIC participants at the start of this cross-sectional study. Between Sept 20, 2017, and Sept 19, 2019, 1094 of 1147 participants were screened for the EDIC Skeletal Health study. 1058 participants completed at least one of a set of DXA scans and were included in the analysis. 47·8% were women and 52·2% were men, 96·6% were White and 3·4% were of other race or ethnicity. The mean age of participants was 59·2 years (SD 6·7). Higher mean HbA1c, higher skin intrinsic fluorescence, and kidney disease (but not retinopathy or neuropathy) were independently associated with a lower total hip BMD. Total hip BMD differed by -10·7 mg/cm2 (95% CI -19·6 to -1·7) for each 1% increase in mean HbA1c, -20·5 mg/cm2 (-29·9 to -11·0) for each 5 unit higher skin intrinsic fluorescence, and -51·7 mg/cm2 (-80·6 to -22·7) in the presence of kidney disease. Similar associations were found for femoral neck and ultra-distal radius BMD, but not for lumbar spine BMD or TBS. Poorer glycaemic control, AGE accumulation, and kidney disease are independent risk factors for lower hip BMD in older adults with type 1 diabetes. Maintenance of glycaemic control and prevention of kidney disease might reduce bone loss and ultimately fractures in this population. Osteoporosis screening might be particularly important in people with these risk factors. Further research to identify AGE blockers could benefit skeletal health. National Institute of Diabetes and Digestive and Kidney Disease.

Performance Analysis of Conventional Machine Learning Algorithms for Diabetic Sensorimotor Polyneuropathy Severity Classification Using Nerve Conduction Studies.

Background Diabetic sensorimotor polyneuropathy (DSPN) is a major form of complication that arises in long-term diabetic patients. Even though the application of machine learning (ML) in disease diagnosis is very common and well-established in the field of research, its application in DSPN diagnosis using nerve conduction studies (NCS), is very limited in the existing literature. Method In this study, the NCS data were collected from the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) clinical trials. The NCS variables are median motor velocity (m/sec), median motor amplitude (mV), median motor F-wave (msec), median sensory velocity (m/sec), median sensory amplitude (μV), Peroneal Motor Velocity (m/sec), peroneal motor amplitude (mv), peroneal motor F-wave (msec), sural sensory velocity (m/sec), and sural sensory amplitude (μV). Three different feature ranking techniques were used to analyze the performance of eight different conventional classifiers. Results The ensemble classifier outperformed other classifiers for the NCS data ranked when all the NCS features were used and provided an accuracy of 93.40%, sensitivity of 91.77%, and specificity of 98.44%. The random forest model exhibited the second-best performance using all the ten features with an accuracy of 93.26%, sensitivity of 91.95%, and specificity of 98.95%. Both ensemble and random forest showed the kappa value 0.82, which indicates that the models are in good agreement with the data and the variables used and are accurate to identify DSPN using these ML models. Conclusion This study suggests that the ensemble classifier using all the ten NCS variables can predict the DSPN severity which can enhance the management of DSPN patients.

Strict glycemic control: a literature review

Diabetes mellitus is a disease that is difficult to control worldwide. Since the better understanding of the pathophysiology of the disease by modern medicine, several ways to control the evolution of the pathology in question have been proposed. As an example, we can mention a study published in 1993 by the Diabetes Control and Complications Trial (DCCT) and, later, in 1998, validated by the United Kingdom Prospective Diabetes Study (UKPDS), which established glycated hemoglobin as one of the main markers evolution and prognosis of the disease. Since the publication of these studies, goals such as: strict glycemic control (corresponding to glycated hemoglobin goals less than or equal to 6.5 mg/dL), have been accepted by the world medical community as references in the control and follow-up of the disease. In this context, the present article has as its guiding question: should strict glycemic control be desired for all patients? Aiming to find out, through literature review, whether glycemic control should be required for all patients. Therefore, a literature review was carried out on published articles on the subject in question, aiming to focus on quaternary prevention and the importance of good clinical practice collaborated by evidence-based medicine. The results indicate that, in the case of strict glycemic control, there is no evidence of benefits in general in its use, being reported in the literature that, in certain populations, especially those over 80 years of age, its use is linked to increased effects. adverse effects and morbidity caused by the disease.