Risk Of Microvascular Complications Research Articles

Abstract #1410803: Continuous Glucose Monitoring and Metrics for Clinical Trials - International Consensus

Randomized controlled trials and other prospective studies for novel interventions in people with diabetes have traditionally reported HbA1c (A1C) values, an estimate of the mean blood glucose for the previous 3 months. This is based on the Diabetes Control and Complications Trial’s established correlation between A1C and risk of microvascular complications. Change in A1C has been used by regulatory agencies for more than 30 years when evaluating diabetes medications’ efficacy. However, with the increasing development of continuous glucose monitoring (CGM), researchers have been increasingly interested in using CGM devices in prospective randomized clinical trials (RCT) to complement A1C and further assess the effects of therapeutic interventions. The diaTribe Foundation invited CGM experts with experience using CGM in clinical trials, FDA, NIH, ADA, and others to become part of this consensus initiative. People with diabetes were also invited. Participation was voluntary and not remunerated. Consolidated draft consensus recommendations and manuscript were developed. Draft materials were then the focus of a meeting in Barcelona, Spain just prior to the 15th ATTD on April 25, 2022. All members of the writing group attended the consensus conference either in person or virtually. The discussion and outcomes from the meeting were used to further refine and revise the consensus recommendations and subsequent manuscript. The final draft was then approved by all members of the writing group. International consensus recommendations include how to optimize CGM-derived glucose data collection in clinical studies: CGM device selection for RCT use, how to report time in range and other metrics, application of CGM sensors in RCT, classification of hypoglycemia or hyperglycemia in RCT, clinically meaningful differences, and CGM data inclusion in the final analysis set. The consensus statement provides recommendations on how to optimize CGM-derived glucose data collection in clinical studies, including CGM-derived glucose metrics that should be used by all researchers and regulatory agencies.

Weight variability and diabetes complications

Body weight is a recognized risk factor for cardiovascular diseases (CVD). More recently, weight variability, i.e. the oscillation of body weight over time, has also been suggested to be independently associated with development of CVD and mortality in subjects without diabetes and in people with both type 1 and type 2 diabetes (T2D). In T2D, weight variability emerged as one of the most relevant risk factors for CVD and it was suggested to interact with the variability of other risk factors to identify people at high cardiovascular risk. In addition, weight variability seems also to confer a higher risk for microvascular complications in people with T2D. While the exact mechanism linking weight variability to CVD is unknown, evidence from experimental models suggests that weight cycling promote an enduring pro-inflammatory program in the adipose tissue. Here we review the clinical evidence relative to the association of weight variability with CVD and microvascular complications of diabetes. We then briefly summarize the alterations proposed to explain this association. Finally, we synthesize the possible strategies, e.g. specific dietetic regimens and available glucose-lowering drugs, to minimize weight fluctuations.

Association between duration of diabetes mellitus and presence as well as severity of diabetic retinopathy among type 2 diabetic patients: A tertiary care hospital based cross-sectional study

Introduction and Aim: Diabetes mellitus (DM) is a large public health problem which is rapidly growing globally as well as in India affecting all age groups. Long duration of diabetes mellitus increases the risk of micro-vascular complications like diabetic retinopathy. The objective was to establish the association between duration of diabetes and presence as well as severity of diabetic retinopathy.
 
 Materials and Methods: The current study was conducted in a tertiary care teaching hospital in Kolkata, approved by the institutional Research and Ethics Committee. In this study, 107 type 2 diabetic patients of 40 years of age and above were selected. Direct ophthalmoscopy (Heine beta-200) was used for detection & grading of diabetic retinopathy (DR).
 
 Results: Results were analyzed using SPSS version 20. Chi square test, Fisher Exact test, Mann Whitney U and Kruskal Wallis test were used in statistical analysis as appropriate. P value less than 0.05 was considered as significant. Significant P values were found in association between duration of diabetes and presence as well as severity of diabetic retinopathy. In binary logistic regression, p value was significant, and odds ratio was 1.089 in case of duration of DM (95% C.I. for Odds Ratio was 1.020-1.164).
 
 Conclusion: Results showed that there was statistically significant association between long duration of diabetes and presence along with severity of diabetic retinopathy.

Weight Loss Versus Glycemic Control as the Primary Treatment Target in Newly Diagnosed Type 2 Diabetes: Why Choose When You Can Have Both?

Weight loss has been associated with significant improvements in glycemic control, quality of life, and comorbidities in people with type 2 diabetes. Furthermore, achieving diabetes remission can reduce the risk of microvascular complications and mitigate the burden of diabetes on healthcare systems. However, preventing weight regain is challenging in the long term. Strict glycemic control, particularly in the early stages of the disease, can reduce the subsequent risk of microvascular complications and specific macrovascular endpoints in the long run; however, its impact on cardiovascular and all-cause mortality remains controversial. New classes of antidiabetic agents, namely glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, have been shown to reduce cardiorenal risk and induce weight loss, in addition to effectively lowering blood glucose with a minimal risk of hypoglycemia. Recently, it has been debated whether weight loss or glycemic control should be the first priority in people with a recent diagnosis of type 2 diabetes. This article aims to discuss the debate from a clinical perspective, evaluate the advantages and disadvantages of each therapeutic strategy, and assess the impact of both approaches on the future risk of diabetic complications, based on the latest evidence. Given that both goals are equally important, the authors suggest that merging the two strategies, with the early and aggressive use of combination therapies consisting of glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, will confer maximum benefits in terms of weight loss and glycemic control, and will reduce the future risk of complications from diabetes. A personalized approach that takes into account specific patient characteristics, including age, sex, race, frailty, and cognitive status, among others, can lead to more effective diabetes care.

Plasma levels of GlycA, a pro-inflammatory glycoprotein biomarker, associate with an increased risk of microvascular complications in patients with type 2 diabetes (Zodiac-62).

GlycA, a pro-inflammatory glycoprotein biomarker, associates with newly developed type 2 diabetes (T2D). We determined the association of plasma GlycA with the development of microvascular complications in patients with established T2D. Plasma GlycA was measured by nuclear magnetic resonance spectrometry in T2D patients without microvascular complications at baseline (n = 145) participating in a longitudinal cohort study of primary care-treated T2D patients (Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study). Associations of GlycA with incident microvascular complications including nephropathy, retinopathy, and neuropathy, were determined by Cox proportional hazards regression analyses. After a median follow-up of 3.2 (interquartile range [IQR]: 2.9-3.4) years, 49 patients (33.8%) developed one or more microvascular complications. Median GlycA levels were 453.5 (IQR: 402.0-512.8) μmol/l. GlycA was associated with incident microvascular complications (hazard ratio [HR] per 1-SD increment: 1.28 [95% confidence interval [CI]:1.00-1.63], P = 0.048]), even after adjustment for potential confounders and high-sensitive C-reactive protein (hs-CRP), HR 1.79 [95%CI:1.25-2.57], P = 0.001). In contrast, hs-CRP levels were not significantly associated with the risk of developing microvascular complications (P = 0.792). Higher plasma GlycA is associated with an increased risk of developing microvascular complications in T2D patients. Altered N-glycan branching associated with acute-phase reactive proteins may represent a preferred biomarker of systemic low-grade inflammation in predicting diabetic complications.

Adherence to a Healthy Lifestyle in Association With Microvascular Complications Among Adults With Type 2 Diabetes

The association between an overall healthy lifestyle and the subsequent risk of microvascular complications among patients with diabetes remains unclear. To examine the association between adherence to a healthy lifestyle before and after diabetes diagnosis and the risk of subsequent microvascular complications among adults with diabetes. This prospective cohort study included incident patients with type 2 diabetes who were free of cardiovascular disease and cancer at the time of diabetes diagnosis and completed the diabetes supplementary questionnaires in the Nurses' Health Study (in 2000 and 2005) and the Health Professionals Follow-Up Study (in 2000, 2004, and 2008) in the US. Data were analyzed from April to August 2021. Diet and lifestyle factors before and after diabetes diagnosis were assessed by validated questionnaires. A healthy lifestyle consisted of nonsmoking, having a healthy body weight (a body mass index of ≥18.5 or <25), engaging in moderate-to-vigorous physical activity (≥150 minutes per week), consuming a high-quality diet (top 40th percentile of the Alternative Healthy Eating Index), and moderate alcohol drinking (5-15 g/d for women and 5-30 g/d for men). Physician-diagnosed microvascular complications including diabetic neuropathy, retinopathy, nephropathy, and foot disorders were self-reported at questionnaire surveys. A total of 7077 patients with type 2 diabetes were included in the cohort (4982 women in NHS and 2095 men in HPFS, mean [SD] age 61 [8.8], 94.2% White). During follow-up, 2878 patients developed microvascular complications. After multivariable adjustment, adherence to a healthy lifestyle before and after diabetes diagnosis were both associated with a lower risk of developing microvascular complications. The relative risk (RR) for participants with 4 or more low-risk lifestyle factors before diabetes diagnosis compared with zero was 0.73 (95% CI, 0.60-0.91) for any microvascular complications, 0.71 (95% CI, 0.54-0.93) for diabetic neuropathy, 0.76 (95% CI, 0.57-1.01) for diabetic retinopathy, 0.42 (95% CI, 0.23-0.79) for diabetic nephropathy, and 0.60 (95% CI, 0.35-1.00) for diabetic foot disorders. Similar results were observed for adherence to a healthy lifestyle after diabetes diagnosis, with an RR of 0.68 (95% CI, 0.55-0.83) for any microvascular complications, 0.67 (95% CI, 0.51-0.88) for diabetic neuropathy, 0.65 (95% CI, 0.48-0.86) for diabetic retinopathy, 0.57 (95% CI, 0.34-0.98) for diabetic nephropathy, and 0.62 (95% CI, 0.37-1.05) for diabetic foot disorders. In addition, greater improvement in lifestyle factors from before to after diabetes diagnosis was also significantly associated with a lower risk of neuropathy or total microvascular complications. Each increment in number of low-risk lifestyle factors was associated with a 6% (RR, 0.94; 95% CI, 0.90-0.98) lower risk for any microvascular complications and a 9% (RR, 0.91; 95% CI, 0.86-0.96) lower risk for diabetic neuropathy. Consistent results were observed when analyses were stratified by age at diabetes diagnosis, sex/cohort, or lifestyle factors before diabetes diagnosis. In this cohort study, adhering to an overall healthy lifestyle was associated with a significantly lower risk of microvascular complications among individuals with diabetes. These findings suggest substantial reduction in the burden of microvascular complications associated with adopting a healthy lifestyle among patients with type 2 diabetes.

Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: A cohort study.

The influence of overall lifestyle behaviors on diabetic microvascular complications remains unknown. In addition, the potential mediating biomarkers underlying the association is unclear. This study aimed to examine the associations of the combined lifestyle factors with risks of total and individual microvascular complications among patients with type 2 diabetes (T2D) and to explore the potential mediation effects of metabolic biomarkers. This retrospective cohort study included 15,104 patients with T2D free of macro- and microvascular complications at baseline (2006 to 2010) from the UK Biobank. Healthy lifestyle behaviors included noncurrent smoking, recommended waist circumference, regular physical activity, healthy diet, and moderate alcohol drinking. Outcomes were ascertained using electronic health records. Over a median of 8.1 years of follow-up, 1,296 cases of the composite microvascular complications occurred, including 558 diabetic retinopathy, 625 diabetic kidney disease, and 315 diabetic neuropathy, with some patients having 2 or 3 microvascular complications simultaneously. After multivariable adjustment for sociodemographic characteristics, history of hypertension, glycemic control, and medication histories, the hazard ratios (95% confidence intervals (CIs)) for the participants adhering 4 to 5 low-risk lifestyle behaviors versus 0 to 1 were 0.65 (0.46, 0.91) for diabetic retinopathy, 0.43 (0.30, 0.61) for diabetic kidney disease, 0.46 (0.29, 0.74) for diabetic neuropathy, and 0.54 (0.43, 0.68) for the composite outcome (all Ps-trend ≤0.01). Further, the population-attributable fraction (95% CIs) of diabetic microvascular complications for poor adherence to the overall healthy lifestyle (<4 low-risk factors) ranged from 25.3% (10.0%, 39.4%) to 39.0% (17.7%, 56.8%). In addition, albumin, HDL-C, triglycerides, apolipoprotein A, C-reactive protein, and HbA1c collectively explained 23.20% (12.70%, 38.50%) of the associations between overall lifestyle behaviors and total diabetic microvascular complications. The key limitation of the current analysis was the potential underreporting of microvascular complications because the cases were identified via electronic health records. Adherence to overall healthy lifestyle behaviors was associated with a significantly lower risk of microvascular complications in patients with T2D, and the favorable associations were partially mediated through improving biomarkers of glycemic control, systemic inflammation, liver function, and lipid profile.

АЛГОРИТМ ОЦЕНКИ РИСКА РАЗВИТИЯ МИКРОСОСУДИСТЫХ ОСЛОЖНЕНИЙ У ПАЦИЕНТОВ С САХАРНЫМ ДИАБЕТОМ 2 ТИПА ДЛЯ СИСТЕМЫ ПОДДЕРЖКИ ПРИНЯТИЯ РЕШЕНИЙ ВРАЧА

Relevance: most experts agree that regular and high-quality dispensary monitoring of patients with diabetes mellitus at the outpatient stage is a necessary condition for preventing the development of vascular complications. The solution of this problem is closely connected with the development and widespread clinical implementation of digital healthcare tools, automated workplaces of doctors, decision support algorithms. Objective: to improve the quality and effectiveness of outpatient care for patients with type 2 diabetes mellitus by digitalizing outpatient admission, using the software of the automated workplace of an endocrinologist (AWPE DM), developing an algorithm for assessing the risk of microvascular complications as an element of a decision support system. Materials and methods: based on the analysis of the results of clinical experience in the use of ARME DM, an algorithm for assessing the risk of microvascular complications has been developed, which allows optimizing the complex of measures for dispensary observation of patients with type 2 diabetes mellitus. Results: demonstrated an increase in the efficiency and quality of medical care for patients with type 2 diabetes mellitus when using AWPE DM in clinical practice; developed a digital algorithm for assessing the risk of microvascular complications, providing stratification of the risks of their development according to the selected criteria for each of the classes; determination of a sufficient minimum of dispensary laboratory and instrumental studies, taking into account the level of credibility of recommendations; personalized correction of therapeutic goals of treatment taking into account the individual characteristics of the patient, including the stage of chronic kidney disease and diabetic retinopathy. Conclusions: the clinical application of the algorithm for assessing the risk of vascular complications, developed taking into account current domestic and foreign clinical recommendations, allows objectively in numerical values to assess the probability of progression of certain classes of microvascular complications of diabetes mellitus in a particular patient, to determine the activities of a personalized program of dispensary observation and rehabilitation. For laboratory and instrumental verification, examinations with the greatest diagnostic significance and suitable for storage and processing in digital format are proposed. Based on the results of the risk assessment directly during the outpatient appointment, the algorithm forms recommendations for the differentiated choice of therapeutic treatment goals, which makes it possible to optimize the personalized program of dispensary observation of the patient.

Frailty and risk of microvascular complications in patients with type 2 diabetes: a population-based cohort study.

Cross-sectional studies found that frailty was associated with prevalent diabetic microvascular complications (DMC). Longitudinal evidence in this regard is inconclusive and insufficient. We aimed to prospectively evaluate the association of pre-frailty and frailty with DMC in patients with type 2 diabetes (T2D). We included 18,062 adults (mean age 59.4 ± 7.2 years, 37.4% female) with T2D at baseline in the UK Biobank. Frailty was defined using the frailty phenotype according to five components (weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength). DMC, defined as diabetic nephropathy, diabetic neuropathy, or diabetic retinopathy, was identified using hospital inpatient records and death registries. Cox proportional hazard regression models considering competing risks were used to evaluate the associations of frailty phenotype with overall DMC events and subtypes. Among all participants, 6101 (33.8%) were classified as non-frail, 10,073 (55.8%) were classified as pre-frail, and 1888 (10.4%) were classified as frail. During a median follow-up of 12.0 years, 3678 DMC cases were documented, including 2213 diabetic nephropathy, 1520 diabetic retinopathy, and 673 diabetic neuropathy events. In the multivariable-adjusted model, compared with participants with non-frail, both pre-frailty and frailty were significantly associated with increased risk of overall DMC (HR 1.10, 95% CI: [1.02, 1.18] for pre-frailty and HR 1.52 [95% CI: 1.36, 1.69] for frailty). Similar results were observed in the subtypes of DMC. For each one-point increase in frailty phenotype score, the risk of overall DMC, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy event increased by 13%, 16%, 10%, and 20%, respectively. Both pre-frailty and frailty were associated with an increased risk of DMC in patients with T2D. These findings have important implications for integrating early assessment and surveillance of frailty in diabetes and may favor the identification of at-risk patients.

ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes.

ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes.

The Impact of Carbamylation and Anemia on HbA1c's Association With Renal Outcomes in Patients With Diabetes and Chronic Kidney Disease.

Glycated hemoglobin (HbA1c) can predict risk for microvascular complications in patients with diabetes. However, HbA1c's reliability in chronic kidney disease (CKD) has been questioned, with concerns including competition from another posttranslational protein modification, carbamylation, acting on the same amino groups as glycation, and anemia with reduced erythrocyte lifespans leading to altered glycation accumulation. We investigated whether carbamylation and anemia modify the impact of HbA1c on renal outcomes in patients with diabetes and CKD. In 1,516 participants from the Chronic Renal Insufficiency Cohort study with diabetes and CKD, Cox regression models were applied to evaluate the association between HbA1c and CKD progression (composite of end-stage kidney disease or 50% decline in estimated glomerular filtration rate [eGFR]), stratified by carbamylated albumin (C-Alb) quartiles and anemia. The mean eGFR was 38.1 mL/min/1.73 m2, mean HbA1c was 7.5% (58 mmol/mol), and median C-Alb was 8.4 mmol/mol. HbA1c was lower in the higher C-Alb quartiles. During a median follow-up of 6.9 years, 763 participants experienced CKD progression. Overall, higher HbA1c was associated with an increased risk of CKD progression (adjusted hazard ratio 1.07 [95% CI 1.02-1.13]). However, using stratified analyses, HbA1c was no longer associated with CKD progression in the highest C-Alb quartile, but did show a monotonic increase in CKD progression risk across each lower C-Alb quartile (P-interaction = 0.022). Anemia also modified the association between HbA1c and CKD progression (P-interaction = 0.025). In patients with coexisting diabetes and CKD, the association between HbA1c and CKD progression is modified by carbamylation and anemia.

Role of neutrophil-to-lymphocyte ratio in predicting microvascular complications in type 2 diabetes mellitus

Background: Tools for early recognition to enable timely intervention and prevention of micro and macrovascular complications are needed in diabetes mellitus. Our study was aimed at assessing the role of neutrophil-to-lymphocyte ratio (NLR) as a tool to identify individuals at risk for microvascular complications in type 2 diabetics, i.e., diabetic nephropathy, retinopathy and neuropathy. Methods: This was a cross-sectional study conducted at a tertiary care hospital in south India that included 98 patients with type 2 diabetes mellitus. NLR was calculated; clinical and laboratory work-up was done in all patients. This was done by quantifying albuminuria by albumin-creatinine ratio (ACR), fundus examination and nerve conduction studies. Correlation between NLR, ACR and other variables was studied in individuals with or without microvascular complications. Results: The NLR in patients with increased ACR was found to be significantly higher when compared to patients with normal ACR (P &lt; 0.001) with a correlation coefficient of 0.783 between ACR and NLR. Receiver operater characteristic curve analysis suggested an NLR cut-off value of 2.032 with a sensitivity and specificity of 89.1% and 81.2%, respectively. A statistically significant higher NLR value was observed in patients with diabetic retinopathy (P = 0.0005) and neuropathy (P &lt; 0.0001). Conclusions: NLR can be used as an early predictor of diabetic nephropathy, neuropathy and retinopathy. It, being an easier tool, can be routinely measured in diabetic individuals to identify at-risk individuals, so that early intervention with appropriate measures can be instituted.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Prospective Study.

Evidence is limited regarding the associations between vitamin D status and microvascular complications in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. In this study we aimed to prospectively investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] and vitamin D receptor (VDR) polymorphisms with risk of diabetic microvascular complications. This analysis included 14,709 participants with T2D who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Median serum 25(OH)D concentration was 40.7 nmol/L (interquartile range 27.5, 56.4). During a median of 11.2 years of follow-up, 1,370 people developed diabetic microvascular complications. Compared with participants with 25(OH)D <25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a multivariable-adjusted HR of 0.65 (95% CI 0.51, 0.84) for composite diabetic microvascular complications, 0.62 (0.40, 0.95) for diabetic retinopathy, 0.56 (0.40, 0.79) for diabetic nephropathy, and 0.48 (0.26, 0.89) for diabetic neuropathy. In addition, in comparisons with participants with 25(OH)D <25 nmol/L and minor allele homozygotes (TT of rs1544410 and GG of rs731236), the multivariable-adjusted HRs of composite diabetic microvascular complications were 0.54 (0.38, 0.78) and 0.55 (0.38, 0.80) for participants with serum 25(OH)D ≥50 nmol/L and major allele homozygotes (CC and AA), respectively, although no significant interaction was observed. Higher serum 25(OH)D concentrations were significantly associated with lower risk of diabetic microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Our findings suggest a potential beneficial role of maintaining adequate vitamin D status in the prevention of diabetic microvascular complications.

Flash glucose monitoring system in special situations.

The management of diabetes mellitus (DM) requires maintaining glycemic control, and patients must keep their blood glucose levels close to the normal range to reduce the risk of microvascular complications and cardiovascular events. While glycated hemoglobin (A1C) is currently the primary measure for glucose management and a key marker for long-term complications, it does not provide information on acute glycemic excursions and overall glycemic variability. These limitations may even be higher in some special situations, thereby compromising A1C accuracy, especially when wider glycemic variability is expected and/or when the glycemic goal is more stringent. To attain adequate glycemic control, continuous glucose monitoring (CGM) is more useful than self-monitoring of blood glucose (SMBG), as it is more convenient and provides a greater amount of data. Flash Glucose Monitoring (isCGM /FGM) is a widely accepted option of CGM for measuring interstitial glucose levels in individuals with DM. However, its application under special conditions, such as pregnancy, patients on hemodialysis, patients with cirrhosis, during hospitalization in the intensive care unit and during physical exercise has not yet been fully validated. This review addresses some of these specific situations in which hypoglycemia should be avoided, or in pregnancy, where strict glycemic control is essential, and the application of isCGM/FGM could alleviate the shortcomings associated with poor glucose control or high glycemic variability, thereby contributing to high-quality care.

HbA1c Variability as an Independent Risk Factor for Microvascular Complications in Type 1 Diabetes.

There are few studies on the role of long-term glycemic variability in complications of type 1 diabetes (T1D). This study was aimed to investigate the associations of HbA1c variability represented by the coefficient of variation of HbA1c with incident microvascular complications in T1D by analyzing the data set from the DCCT/EDIC study. Patients (n = 1240) were divided into four groups by HbA1c variability quartiles. Incident microvascular complications were assessed for a duration of an average of 20.5 years. Multivariable models were performed to examine the associations between HbA1c variability and incident microvascular complications. All incident microvascular complications were higher in the fourth quartile of the HbA1c variability group. After adjusting for clinical risk factors, HbA1c variability was positively associated with a higher risk of all diabetic microvascular complications (P < .05). Specifically, it had 1.125 (1.082-1.170), 1.114 (1.074-1.154), 1.061 (1.024-1.099), or 1.088 (1.052-1.125) times higher odds (95% confidence interval [CI]) of having retinopathy, nephropathy, clinical neuropathy, or autonomic neuropathy, independent of mean HbA1c values (P < .05). Furthermore, there were higher incident microvascular complications with higher HbA1c variability when HbA1c value was above the group median of 7.9%, while only higher incident autonomic neuropathy with higher HbA1c variability when HbA1c was below the group median. Our results showed a significant independent association between HbA1c variability and the risk of microvascular complications in T1D. HbA1c variability might be a supplemental risk stratification tool to mean HbA1c for microvascular complications in T1D.

Association of prediabetes with death and diabetic complications in older adults: the pros and cons of active screening for prediabetes.

active screening can improve health outcomes for people with prediabetes. However, its efficacy in older adults remains uncertain. the study aimed to analyse the progression from prediabetes to diabetes in older adults, including associated complications and mortality rates, to determine the benefits of active screening. retrospective cohort study. Korean National Health Insurance Service claims database. a total of 36,946 adults aged ≥65years who underwent national health examinations from 2006 to 2008. follow-up was until 31 December 2015. Cox's proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for death and diabetic complications. over a median follow-up of 8.2years, 19.3% of older adults with prediabetes progressed to diabetes. Compared with normoglycaemic adults, the multivariable-adjusted HRs (95% CI) for major adverse cardiovascular events were 1.01 (0.95-1.07), 1.08 (0.95-1.23), 1.14 (1.05-1.23) and 1.50 (1.35-1.68) in adults with prediabetes, newly diagnosed diabetes, diabetes not on insulin and diabetes on insulin, respectively. The corresponding HRs (95% CI) for diabetic retinopathy risk were 1.28 (1.15-1.43), 3.16 (2.71-3.69), 6.58 (6.02-7.19) and 9.17 (8.21-10.24). Diabetic nephropathy risk also significantly increased. progression from prediabetes to diabetes is an important concern among older adults. Prediabetes is associated with the risk of microvascular complications, but not cardiovascular complications and mortality. Therefore, active regular screening for prediabetes is necessary to prevent microvascular complications.

665-P: Awareness of Time in Range Varies by Type of Health Care Provider

Background and Aims: Previous studies have shown an association between Time in Range (TIR) and risk of microvascular complications, but TIR is not used widely in diabetes care. This study aimed to assess differences in awareness and use of TIR among healthcare providers (HCPs) . Methods: In an online survey in September 2021, 303 HCPs, each working with a minimum of 30 patients with diabetes each month, were asked a series of questions related to challenges, evaluation, and goal-setting when discussing diabetes management with patients. Respondents were classified as either Endocrinologists (Endo) , Diabetes Educators (DE) , or primary care providers (PCP) . Statistical significance was tested at the 95% confidence level (p&amp;lt;0.05) . Results: DEs were more likely to be aware of (96%, n=106) and use (94%, n=106) TIR in clinical practice than Endos (92%, 88%, n=98) and PCPs (56%, 46%, n=99) . Among respondents who were aware of TIR (n=247) , Endos were more likely to use TIR when making treatment decisions (87%, n=90) than PCPs (69%, n=55) . Among those who reported using TIR in clinical practice (n=234) , PCPs were least familiar (67%, n=46) with CGM metrics compared to Endos (91%, n=88) and DEs (79%, n=100) . Conclusions: This data highlights differences in TIR use between Endos, DEs, and PCPs, and the lower levels of TIR awareness among PCPs. This study emphasizes opportunities for increased awareness of TIR through education and training of PCPs on CGM and TIR. Disclosure J.Kenney: None. A.Briskin: None. J.Tait: Employee; dQ&amp;A. E.Shoger: Other Relationship; Diabetes industry. R.Wood: Other Relationship; Multiple companies and patient organizations (&amp;gt;10) . A.L.Peters: Advisory Panel; Abbott Diabetes, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Shouti, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Other Relationship; Omada Health, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust, Stock/Shareholder; Teladoc Health.

666-P: CGM Access Is the Main Barrier to TIR Use among Providers

Background and Aims: Previous studies have shown a correlation between Time in Range (TIR) and risk for microvascular complications, but the metric is not used widely in diabetes care. This study aimed to assess the barriers to TIR use among healthcare providers. Methods: In an online survey in September 2021, 303 HCPs, each working with a minimum of 30 patients with diabetes each month, were asked a series of questions related to challenges, evaluation, and goal-setting when discussing diabetes management with their patients. Respondents were classified as either Endocrinologists (Endo) , Diabetes Educators (DE) , or primary care providers (PCP) . Statistical significance was tested at the 95% confidence level (p&amp;lt;0.05) . Results: 80% of HCPs who use TIR (n=234) identify access to CGM as a main drawback of TIR and 72% (n=289) identified cost as a downside of CGM use. When TIR non-users (n=64) were asked what would convince them to use TIR with patients, 41% cited increased access to CGM and 30% cited training and resources about how to use TIR data. 83% of non-users (n=64) believe TIR would be useful in their diabetes care. When asked what would improve their diabetes care, 39% of HCPs said having more patients on CGM and 28% said the ability to use TIR data with more patients (n=246) . Conclusions: This data highlights the barriers to TIR adoption and use among HCPs. Increased access to CGM and education on TIR use in clinical practice can help advance TIR in diabetes care. Disclosure J.Kenney: None. J.Tait: Employee; dQ&amp;A. A.Briskin: None. E.Shoger: Other Relationship; Diabetes industry. R.Wood: Other Relationship; Multiple companies and patient organizations (&amp;gt;10) . A.L.Peters: Advisory Panel; Abbott Diabetes, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Shouti, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Other Relationship; Omada Health, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust, Stock/Shareholder; Teladoc Health.

The prognostic role of extended preoperative hypercoagulability work-up in high-risk microsurgical free flaps: a single-center retrospective case series of patients with heterozygotic factor V Leiden thrombophilia

IntroductionHypercoagulability is associated with an increased risk of microvascular complications and free flap failures. The authors present their experience and approach to diagnosing and treating patients with heterozygotic factor V Leiden (hFVL) thrombophilia undergoing free flap reconstruction.MethodsBetween November 2009 and June 2018, 23 free flap surgeries were performed in 15 hypercoagulable patients with hFVL. According to the timing of perioperative hypercoagulability work-up, they were grouped into flaps with established diagnoses prior to surgery (Group A) versus flaps with unknown diagnoses prior to surgery (Group B). Baseline characteristics and perioperative complications were compared between both groups, including revision surgeries due to microvascular thromboses, acute bleedings, hematomas, flap necroses, and reconstructive failures.ResultsHFVL mutations had been confirmed preoperatively in 14 free flap surgeries (61%, Group A), whereas in 9 free flap surgeries (39%, Group B), mutations were only diagnosed postoperatively after the occurrence of microvascular thromboses had warranted extended hypercoagulability work-up. The overall rate of intraoperative flap thromboses was 9% (n = 2), whereas the overall rate of postoperative flap thromboses was 43% (n = 10). The corresponding salvage rates were 100% (n = 2/2) for intraoperative and 40% (n = 4/10) for postoperative pedicle thromboses. A total of five free flaps were lost (22%). Upon comparison, flaps with an unconfirmed diagnosis prior to surgery were at ten times higher risk for developing total necroses (flaps lost in Group B = 4/9 versus Group A = 1/14; OR: 10.4; 95% CI 1.0, 134.7; p = 0.03).ConclusionMeticulous preoperative work-up of patients with any history of hypercoagulability can help reduce free flap loss rates, thus improving surgical outcomes and increasing patient safety.

Precision diagnostic approach to predict 5-year risk for microvascular complications in type 1 diabetes.

SummaryBackgroundIndividuals with long standing diabetes duration can experience damage to small microvascular blood vessels leading to diabetes complications (DCs) and increased mortality. Precision diagnostic tailors a diagnosis to an individual by using biomedical information. Blood small molecule profiling coupled with machine learning (ML) can facilitate the goals of precision diagnostics, including earlier diagnosis and individualized risk scoring.MethodsUsing data in a cohort of 537 adults with type 1 diabetes (T1D) we predicted five-year progression to DCs. Prediction models were computed first with clinical risk factors at baseline and then with clinical risk factors and blood-derived molecular data at baseline. Progression of diabetic kidney disease and diabetic retinopathy were predicted in two complication-specific models.FindingsThe model predicts the progression to diabetic kidney disease with accuracy: 0.96 ± 0.25 and 0.96 ± 0.06 area under curve, AUC, with clinical measurements and with small molecule predictors respectively and highlighted main predictors to be albuminuria, glomerular filtration rate, retinopathy status at baseline, sugar derivatives and ketones. For diabetic retinopathy, AUC 0.75 ± 0.14 and 0.79 ± 0.16 with clinical measurements and with small molecule predictors respectively and highlighted key predictors, albuminuria, glomerular filtration rate and retinopathy status at baseline. Individual risk scores were built to visualize results.InterpretationWith further validation ML tools could facilitate the implementation of precision diagnosis in the clinic. It is envisaged that patients could be screened for complications, before these occur, thus preserving healthy life-years for persons with diabetes.FundingThis study has been financially supported by Novo Nordisk Foundation grant NNF14OC0013659.