Risk Of Microvascular Complications Research Articles

Development and external validation of an algorithm for self-identification of risk for microvascular complications in patients with type 1 diabetes.

Microvascular complications, such as diabetic retinopathy (DR), diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN), are common and serious outcomes of inadequately managed type 1 diabetes (T1D). Timely detection and intervention in these complications are crucial for improving patient outcomes. This study aimed to develop and externally validate machine learning (ML) models for self-identification of microvascular complication risks in T1D population. Utilizing data from the Chinese Type 1 Diabetes Comprehensive Care Pathway program, 911 T1D patients and 15 patient self-reported variables were included. Combined with XGBoost algorithm and cross-validation, self-identification models were constructed with 5 variables selected by feature importance ranking. For external validation, an online survey was conducted within a nationwide T1D online community (N = 157). The area under the receiver-operating-characteristic curve (AUROC) was adopted as the main metric to evaluate the model performance. The SHapley Additive exPlanation was utilized for model interpretation. The prevalence rates of microvascular complications in the development set and external validation set were as follows: DR 7.0% and 12.7% (p = 0.013), DN 5.9% and 3.2% (p = 0.162) and DPN 10.5% and 20.4% (p < 0.001). The models demonstrated the AUROC values of 0.889 for DR, 0.844 for DN and 0.839 for DPN during internal validation. For external validation, the AUROC values achieved 0.762 for DR, 0.718 for DN and 0.721 for DPN. ML models, based on self-reported data, have the potential to serve as a self-identification tool, empowering T1D patients to understand their risks outside of hospital settings and encourage early engagement with healthcare services.

Effects of Neoadjuvant Radiation and Recipient Vessel Characteristics on Microvascular Complication Rates in Reconstruction of Lower Extremity Soft-Tissue Sarcoma Defects.

The treatment approach for soft-tissue sarcomas (STS) of the lower extremity has shifted toward the use of neoadjuvant radiation combined with limb-sparing surgery (LSS). The resulting defects often require reconstruction with free tissue transfer for adequate outcomes. Data has demonstrated a potential increased risk of microvascular complications for free flaps performed using irradiated recipient vessels. Similarly, certain anatomic areas of the lower extremity have a high proportion of unnamed perforators that are available as recipient vessels, increasing the technical difficulty. We aimed to determine if the characteristics of recipient vessels that were used for reconstruction of STS defects influenced rates of microvascular complications in our patients. A retrospective chart review of all patients who underwent reconstruction of lower extremity STS defects with free tissue transfer from 2009-2020 was conducted. Data regarding recipient vessel type (axial vessel vs. unnamed perforator), radiation status of the recipient vessels (irradiated vs. non-irradiated), and microvascular complications was compared across groups. A total of 204 free flaps were included. The overall microvascular complication rate was 13.7% (28 cases). Most microvascular complications were detected postoperatively (82.1%) rather than intraoperatively, with the majority involving venous congestion/thrombosis (20 cases, 71.4%). While there was a trend toward increased microvascular complications with the use of irradiated recipient vessels (27 cases, 96.4%), this did not reach statistical significance (OR = 1.98, p = 0.52). The use of perforating branches as recipient vessels did not confer increased risk of microvascular complications (OR = 0.87, p = 0.75). Reconstruction of irradiated lower extremity STS defects represents a particularly challenging issue. This analysis demonstrates that free tissue transfer can be safely performed using irradiated vessels without significant increased risk of microvascular complications. Furthermore, unnamed perforating branches can also be successfully used for reconstruction in anatomically challenging areas of the lower extremity.

Type 2 diabetes complications in ethnic minority compared with European host populations: a systematic review and meta-analysis

This systematic review and meta-analysis aimed to quantify differences in type 2 diabetes (T2D) complications between ethnic minority populations and European host populations, in both cross-sectional and prospective studies. Following...

Management Strategies for Young-Onset Type 2 Diabetes Mellitus: An Integrated Approach

The prevalence of young-onset type 2 diabetes is increasing rapidly worldwide along with the incidence of obesity, including in Korea. Compared with later onset type 2 diabetes, patients with young-onset type 2 diabetes have a higher risk of microvascular complication, macrovascular complication, and disease-related mortality. Thus, integrated attention and management of associated pathobiological, socioeconomic, and mental health factors are needed. Based on the very few evidence-based studies in management, in this review, we describe strategies for the integrated management for young-onset type 2 diabetes.

Lipids and apolipoproteins and the risk of vascular disease and mortality outcomes in women and men with type 2 diabetes in the ADVANCE study.

Whether apolipoproteins (apolipoprotein A1, apolipoprotein B, apolipoprotein B/apolipoprotein A1 [ApoB/ApoA1] ratio) or very-low-density lipoprotein (VLDL) cholesterol are better risk predictors than established lipid risk markers, and whether there are sex differences, is uncertain, both in general populations and in patients with diabetes. The aim of this study was to assess the association between established risk markers, apolipoproteins and the risk of macro- and microvascular disease and death in a large study of women and men with diabetes and to assess the potential sex differences in the associations. Established lipid risk markers were studied in 11 140 individuals with type 2 diabetes from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial, and apolipoproteins (A1, B, ApoB/ApoA1 ratio) and VLDL cholesterol from nuclear magnetic resonance (NMR) lipid analyses in biobanked samples from 3586 individuals included in the ADVANCE case-cohort study (ADVANCE CC). Primary outcomes were major macro- and microvascular events and death. Cox proportional hazards models adjusted for confounders were used to quantify the associations (hazard ratio [HR] and 95% confidence intervals [CIs]) between established lipid risk markers and apolipoproteins with study outcomes. To address potential effect modification by sex, we investigated the association between the lipid risk markers and outcomes in subgroup analyses by sex. There was a lower risk of macrovascular complications for high-density lipoprotein (HDL) cholesterol (HR [95%CI] 0.88 [0.82-0.95]), a higher risk for total cholesterol (1.10 [1.04-1.17]), low-density lipoprotein (LDL) cholesterol (1.15 [1.08-1.22]), non-HDL cholesterol (1.13 [1.07-1.20]) and the total cholesterol/HDL ratio (1.20 [1.14-1.27]) but no significant associations with triglycerides from ADVANCE. There was a higher risk of macrovascular complications for the ApoB/ApoA1 ratio (1.13 [1.03-1.24]) from the ADVANCE CC. Only the ApoB/ApoA1 ratio (1.19 [1.06-1.34]), but none of the established lipid risk markers, was associated with a higher risk of microvascular complications. There were no statistically significant sex differences for any of the established lipid risk markers or apolipoproteins with any outcome. Using C-statistics and net reclassification improvement (NRI) did not detect significant improvement in predicting all outcomes by adding lipids or apolipoproteins to the models with confounding factors only. All established lipid risk markers, except triglycerides, were predictors of macrovascular complications, but not microvascular complications, in patients with type 2 diabetes. The ApoB/ApoA1 ratio was associated with major macro- and microvascular complications, but there was no evidence that apolipoproteins are better than established lipid risk markers in predicting cardiovascular complications in patients with type 2 diabetes.

Posttraumatic Stress Disorder and Type 2 Diabetes Outcomes in Veterans

Posttraumatic stress disorder (PTSD) symptom reduction is linked with lower risk of incident type 2 diabetes (T2D), but little is known about the association between PTSD and comorbid T2D outcomes. Whether PTSD is a modifiable risk factor for adverse T2D outcomes is unknown. To determine whether patients with PTSD who improved and no longer met diagnostic criteria for PTSD had a lower risk of adverse T2D outcomes compared with patients with persistent PTSD. This retrospective cohort study used deidentified data from US Veterans Health Administration (VHA) historical medical records (from October 1, 2011, to September 30, 2022) to create a cohort of patients aged 18 to 80 years with comorbid PTSD and T2D. Data analysis was performed from March 1 to June 1, 2024. Diagnoses of PTSD and T2D. The main outcomes were insulin initiation, poor glycemic control, any microvascular complication, and all-cause mortality. Improvement of PTSD was defined as no longer meeting PTSD diagnostic criteria, per a PTSD Checklist score of less than 33. Entropy balancing controlled for confounding. Survival and competing risk models estimated the association between meeting PTSD criteria and T2D outcomes. Subgroup analyses examined variation by age, sex, race, PTSD severity, and comorbid depression status. The study cohort included 10 002 veterans. More than half of patients (65.3%) were aged older than 50 years and most (87.2%) were men. Patients identified as Black (31.6%), White (62.7%), or other race (5.7%). Before controlling for confounding with entropy balancing, patients who no longer met PTSD diagnostic criteria had similar incidence rates for starting insulin (22.4 vs 24.4 per 1000 person-years), poor glycemic control (137.1 vs 133.7 per 1000 person-years), any microvascular complication (108.4 vs 104.8 per 1000 person-years), and all-cause mortality (11.2 vs 11.0 per 1000 person-years) compared with patients with persistent PTSD. After controlling for confounding, no longer meeting PTSD criteria was associated with a lower risk of microvascular complications (hazard ratio [HR], 0.92 [95% CI, 0.85-0.99]). Among veterans aged 18 to 49 years, no longer meeting PTSD criteria was associated with a lower risk of insulin initiation (HR, 0.69 [95% CI, 0.53-0.88]) and all-cause mortality (HR, 0.39 [95% CI, 0.19-0.83]). Among patients without depression, no longer meeting PTSD criteria was associated with a lower risk of insulin initiation (HR, 0.73 [95% CI, 0.55-0.97]). The findings of this cohort study of patients with comorbid PTSD and T2D suggest that PTSD is a modifiable risk factor associated with a modest reduction in microvascular complications. Further research is needed to determine whether findings are similar in non-VHA health care settings.

Association of ultraprocessed food consumption with risk of microvascular complications among individuals with type 2 diabetes in the UK Biobank: a prospective cohort study

BackgroundThe poor nutritional characteristics and potentially harmful molecules in ultraprocessed foods (UPFs) are risk factors for diabetic microvascular complications. However, the evidence regarding UPFs and diabetic microvascular complications remains limited. ObjectivesWe aimed to evaluate the associations between UPF consumption and risk of diabetic microvascular complications, to examine the underlying biological pathways (e.g., inflammation and lipid profile), and to identify whether the associations differ by type of UPF dietary patterns. MethodsWe included a prospective cohort of UK Biobank participants with type 2 diabetes (T2D) having at least one 24-h dietary recall (N = 5685). UPFs were defined using the Nova classification. Principal component analysis was used to derive UPF consumption patterns. Associations of UPFs and their consumption patterns with microvascular complications were assessed using Cox proportional hazards regression models. Mediation analyses were used to estimate the mediating effects of 22 biomarkers. ResultsDuring a median of 12.7 y of follow-up, 1243 composite microvascular complications events occurred (599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events). Five consumption patterns were identified (spread and bread, cereal prepared with liquids, dairy-based products, sugary beverage and snack, and mixed beverage and savory snack patterns). A 10% increment in the proportion of UPF was associated with higher hazards of the composite microvascular complications (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.03, 1.13) and diabetic kidney disease (HR: 1.13; 95% CI: 1.06, 1.20). Triglycerides, C-reactive protein, and body mass index collectively explained 22.0% (9.6%–43.0%) of the association between UPF intake and composite microvascular complications. Pattern high in mixed beverage and savory snack was associated with a higher risk of composite microvascular complications. ConclusionsHigher UPF consumption was associated with higher risks of diabetic microvascular complications, and the association was partly mediated through multiple potential ways.

Social Isolation, Loneliness, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes Mellitus

Rationale & ObjectiveSocial disconnection has been associated with poor cardiometabolic health. This study sought to investigate the associations of social isolation and loneliness with diabetic microvascular complications (DMC) among individuals with type 2 diabetes mellitus (T2DM) and compare these associations to those related to traditional risk factors. Study DesignProspective cohort study. Setting & ParticipantsA total of 24,297 UK Biobank participants with T2DM and no DMC at baseline. ExposureSocial isolation and loneliness measured using self-reported questionnaires. OutcomeThe incidence of DMC defined as a composite of diabetic kidney disease, diabetic retinopathy, or diabetic neuropathy. Analytical ApproachMultivariable cause-specific hazards regression. To compare the relative importance of social disconnection with other established factors, the R2 values of the Cox models were calculated. ResultsDuring a median follow-up of 12.6 years, 5,530 patients were documented to develop DMC (3,458 with diabetic kidney disease, 2,255 with diabetic retinopathy, and 1,146 with diabetic neuropathy). The highest level of social isolation was associated with an increased risk of any DMC component (most vs. least: HR: 1.13; 95% CI: 1.05-1.22), especially diabetic kidney disease (HR: 1.14, 95% CI: 1.04-1.25) and neuropathy (HR: 1.31, 95% CI: 1.11-1.53). Any level of loneliness was associated with an increased risk of any DMC component (HR: 1.12; 95% CI: 1.02-1.23) and diabetic kidney disease (HR: 1.16, 95% CI: 1.03-1.30). Social isolation and loneliness exhibited associations with DMC comparable to other conventional risk factors including smoking, blood pressure, and physical activity. LimitationsLimited generalizability related to the composition of participants in the UK Biobank Study. ConclusionsSocial isolation and loneliness were independently associated with a higher risk of incident DMC among individuals with T2DM, with comparable importance to other traditional risk factors. These findings underscore social isolation and loneliness as novel and potentially modifiable risk factors for DMC.

Diabetes-Related Macrovascular Complications Are Associated With an Increased Risk of Diabetic Microvascular Complications: A Prospective Study of 1518 Patients With Type 1 Diabetes and 20 802 Patients With Type 2 Diabetes in the UK Biobank.

Diabetic vascular complications share common pathophysiological mechanisms, but the relationship between diabetes-related macrovascular complications (MacroVCs) and incident diabetic microvascular complications remains unclear. We aimed to investigate the impact of MacroVCs on the risk of microvascular complications. There were 1518 participants with type 1 diabetes (T1D) and 20 802 participants with type 2 diabetes from the UK Biobank included in this longitudinal cohort study. MacroVCs were defined by the presence of macrovascular diseases diagnosed after diabetes at recruitment, including coronary heart disease, peripheral artery disease, stroke, and ≥2 MacroVCs. The primary outcome was incident microvascular complications, a composite of diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy. During a median (interquartile range) follow-up of 11.61 (5.84-13.12) years and 12.2 (9.50-13.18) years, 596 (39.3%) and 4113 (19.8%) participants developed a primary outcome in T1D and type 2 diabetes, respectively. After full adjustment for conventional risk factors, Cox regression models showed significant associations between individual as well as cumulative MacroVCs and the primary outcome, except for coronary heart disease in T1D (T1D: diabetes coronary heart disease: 1.25 [0.98-1.60]; diabetes peripheral artery disease: 3.00 [1.86-4.84]; diabetes stroke: 1.71 [1.08-2.72]; ≥2: 2.57 [1.66-3.99]; type 2 diabetes: diabetes coronary heart disease: 1.59 [1.38-1.82]; diabetes peripheral artery disease: 1.60 [1.01-2.54]; diabetes stroke: 1.50 [1.13-1.99]; ≥2: 2.66 [1.92-3.68]). Subgroup analysis showed that strict glycemic (glycated hemoglobin <6.5%) and blood pressure (<140/90 mm Hg) control attenuated the association. Individual and cumulative MacroVCs confer significant risk of incident microvascular complications in patients with T1D and type 2 diabetes. Our results may facilitate cost-effective high-risk population identification and development of precise prevention strategies.

A GENETIC RISK SCORE OF EARLY-ONSET TYPE 2 DIABETES PREDICTS EARLY DEATH AND BENEFITS OF INTENSIVE GLYCEMIC CONTROL IN ADVANCE TRIAL

Objective: Context: Early-onset type 2 diabetes (T2D) increases rapidly worldwide, alongside obesity, and carries an excess risk of microvascular complications and early death compared to when it started later in life. We have developed a multi-polygenic risk score (multiPRS) that predicts the risk of major micro- and macrovascular complications of T2D. We showed that individuals with high multiPRS scores for macrovascular events benefited more from tight blood pressure control while those with high multiPRS scores for microvascular events benefited from glycemic control. Early-onset T2D is genetically determined. Objective: To develop a genetic risk score that identifies individuals who are more susceptible to early-onset T2D and assess whether they could benefit from tight glycemic control. Design and method: We developed a genetic risk score (GRS) composed of 22 SNPs associated with early-onset T2D. We analysed 545 participants of European descent of ADVANCE with the highest GRS values and 526 subjects with the lowest GRS for early-onset T2D. Results: The median age at diagnosis of T2D was 54.9 in the high GRS and 64.6 in the low GRS group. Compared to participants with low GRS, those with high GRS were slightly heavier with a BMI of 30.8 (5.1 SD) vs 29.6 (4.9 SD), p = 7.2 x 10-5, they received more antidiabetic drugs (n= 1.5 (0.8) vs 1.2 (0.8), p = 1.2 x 10-7) and they died 5.7 years earlier (70.8 vs 76.5 years old p = 9 x 10-7). Contrary to the low GRS group, intensive glycemic control reduced mortality significantly in the high GRS group. Combination of intensive blood pressure and glycemia control led to a relative risk reduction of 52% (p = 0.028) and a number needed to treat of only 10 in the high GRS group while no significant effects were observed in the low GRS group. Conclusions: This novel GRS can identify individuals at risk of early-onset T2D who can benefit from tight glycemic control while its combination with blood pressure control is the most effective in reducing cardiorenal outcomes and death rate.

Exploring potential correlations between HLA class II and the risk of microvascular complications in Japanese patients with type 1 diabetes

Managing complications in Type 1 diabetes (T1D) remains challenging. HLA genes, particularly DR and DQ, are linked to T1D susceptibility. We studied 48 Japanese T1D inpatients and revealed associations between DRB1*04:05-DQB1*04:01 and DRB1*09:01-DQB1*03:03 haplotypes and complications, offering a new perspective for future research.

Relationship Between Triglyceride-Glucose Index and Microvascular Complications in Hospitalized Patients with Type 2 Diabetes Mellitus

Aim: The increasing prevalence of diabetes mellitus (DM) brings about a rise in nephropathy, retinopathy, and neuropathy, which are microvascular complications of diabetes. The triglyceride-glucose (TyG) index is a convenient indicator of insulin resistance. It is related to microvascular and macrovascular complications among nonhospitalized patients with diabetes. However, it is unclear if the TyG index poses risks for vascular complications of type 2 DM in hospitalized patients. This study aims to investigate possible relations between this index and the risk of microvascular complications in hospitalized patients with type 2 DM. Material and Methods: The present study included 420 type 2 DM patients who were hospitalized in our clinic between February 2019 and May 2022. The TyG index was measured as fasting triglycerides mg/dL × fasting glucose mg/dL/2. The presence of microalbuminuria (MAU), diabetic neuropathy, chronic kidney disease (CKD), and retinopathy (DR) were evaluated. The data were analzed using IBM SPSS 22.0 statistical software. The level of statistical significance was taken as p

Associations Between Beverage Consumption and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes.

The relationship between the consumption of different beverages and the risk of microvascular complications in individuals with type 2 diabetes (T2D) is unclear. To investigate the association of individual beverage consumption, including artificially sweetened beverages (ASBs), sugar-sweetened beverages (SSBs), tea, coffee, natural juice, and yogurt, with the risk of microvascular complications in adults with T2D. This cohort study included 6676 participants with T2D who were free of macrovascular and microvascular complications at baseline in the UK Biobank. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 11.7 years, 1116 cases of composite microvascular complications were documented. After multivariable adjustment, a linear dose-response relationship was demonstrated between the consumption of ASBs and SSBs and the risk of microvascular complications. Compared with nonconsumers, those who consumed ≥2.0 units/day of ASBs and SSBs had an HR (95% CI) of 1.44 (1.18-1.75) and 1.32 (1.00-1.76) for composite microvascular complications, respectively. In addition, higher tea consumption was associated with a lower risk of diabetic retinopathy, with an HR (95% CI) of 0.72 (0.57-0.92) for whom consuming ≥4.0 units/day. There was no significant association between individual beverage consumption and the risk of diabetic neuropathy. No significant association was observed between the consumption of coffee, natural juice, or yogurt and the risks of microvascular complications. Moreover, substituting half units/day of ASBs or SSBs with tea or coffee was associated with a 16% to 28% lower risk of microvascular complications. Higher consumption of ASBs and SSBs was linearly associated with an increased risk of microvascular complications in adults with T2D.

Long-term exposure to ambient air pollution and risk of microvascular complications among patients with type 2 diabetes: a prospective study.

Patients with type 2 diabetes (T2D) may disproportionately suffer the adverse cardiovascular effects of air pollution, but relevant evidence on microvascular outcome is lacking. We aimed to examine the association between air pollution exposure and the risk of microvascular complications among patients with T2D. This prospective study included 17 995 participants with T2D who were free of macro- and micro-vascular complications at baseline from the UK Biobank. Annual average concentrations of particulate matter (PM) with diameters <2.5 μm (PM2.5), <10 μm (PM10), nitrogen dioxide (NO2) and nitrogen oxides (NOx) were assessed using land use regression models. Cox proportional hazards regression was used to estimate the associations of air pollution exposure with incident diabetic microvascular complications. The joint effects of the air pollutant mixture were examined using quantile-based g-computation in a survival setting. In single-pollutant models, the adjusted hazard ratios (95% confidence intervals) for composite diabetic microvascular complications per interquartile range increase in PM2.5, PM10, NO2 and NOx were 1.09 (1.04-1.14), 1.06 (1.01-1.11), 1.07 (1.02-1.12) and 1.04 (1.00-1.08), respectively. Similar significant results were found for diabetic nephropathy and diabetic neuropathy, but not for diabetic retinopathy. The associations of certain air pollutants with composite microvascular complications and diabetic nephropathy were present even at concentrations below the World Health Organization limit values. Multi-pollutant analyses demonstrated that PM2.5 contributed most to the elevated risk associated with the air pollutant mixture. In addition, we found no interactions between air pollution and metabolic risk factor control on the risk of diabetic microvascular complications. Long-term individual and joint exposure to PM2.5, PM10, NO2 and NOx, even at low levels, was associated with an increased risk of diabetic microvascular complications, with PM2.5 potentially being the main contributor.

Knowledge, attitudes and practices towards glycemic control among persons with diabetes mellitus at two tertiary hospitals in Uganda.

Intensive glycaemic control reduces the risk of microvascular complications in persons with diabetes mellitus (DM). Owing to limited data available, we aimed to determine the knowledge, attitude, and practices (KAPs) toward glycaemic control among Ugandans with DM at two large tertiary healthcare facilities. A cross-sectional study was conducted among persons with DM attending outpatient clinics at Kiruddu National Referral Hospital (KNRH) and Mulago National Specialized Hospital (MNSH) between March and April 2022. Eligible participants provided written informed consent and were recruited through a systematic sampling technique and relevant data was collected using a pretested, interviewer-administered, semi-structured questionnaire. Of the 452 participants, 318 (70.4%) were females. The median age was 52 years (IQR: 45-60 years), with more than two-thirds diagnosed with DM at ≥36 years (69.8%, n=310). Overall, 274 participants (60.6%) had good knowledge on glycemic control. At multivariable logistic regression analysis, good knowledge about glycaemic control was significantly associated with having received training on glycaemic control (aOR: 2.3, 95% CI: 1.4 - 3.7, p=0.002), level of education: diploma (aOR: 4.3, 95% CI: 1.1 - 17.8, p=0.042), degree aOR: 4.9, 95% CI: 1.0 - 23.1, p=0.046) compared to informal education, and nearest distance from the health facility (aOR: 3.1, 95% CI: 1.0 - 9.6, p=0.047). More than half of the patients had good knowledge about glycaemic control and this was associated with level of education, distance from the health facility and having received training. Further studies assessing the correlations between actual level of glycaemic control and patient related KAPs are recommended.

Cardiovascular health metrics defined by Life's Essential 8 scores and subsequent macrovascular and microvascular complications in individuals with type 2 diabetes: A prospective cohort study.

To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non-high-density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. During a median follow-up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10-point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47-0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53-0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications.

Management of Early-Onset Type 2 Diabetes

Early-onset type 2 diabetes is experiencing a rapid global increase, coinciding with the escalating rates of obesity. In contrast to diagnoses later in life, an earlier diagnosis is associated with unexplained excess risk of microvascular complications, adverse cardiovascular outcomes, and premature mortality. Patients with early-onset type 2 diabetes appear to undergo a more aggressive clinical course, which can be exacerbated by the limited availability of treatments. The heightened burden of complications places individuals with early-onset type 2 diabetes at a substantial risk of multimorbidity, underscoring the urgency for interventions to reverse these concerning trends. While the pathophysiology and interventions for adolescent-onset (&lt; 19 years) type 2 diabetes within the early-onset cohort have received considerable attention in research, young adults aged 19~39 years (a larger proportion numerically) remain insufficiently characterized and are notably absent in the current evidence guiding management. Current management approaches derived from trials in later-onset type 2 diabetes may not be suited for this specific demographic. This review provides a comprehensive summary of recent findings related to early-onset type 2 diabetes, aiming to contribute valuable insights that could shape future strategies for prevention, diagnosis, and treatment.

Abstract P423: Individual and Combined Effects of Diet, Exercise, and Metformin on Risk of Microvascular Complications in Older Type 2 Diabetes Patients: Post-Hoc Analysis of Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial Data

Introduction: Microvascular complications are a major burden on the health of type 2 diabetes (T2D) patients. The literature has yielded mixed results regarding synergistic effects of common diabetes treatments (i.e., metformin, exercise, and diet) on microvascular complication risk. Some trials demonstrated that the combination of metformin and exercise diminished beneficial effects. We aimed to explore this ambiguity in findings by examining the effects of metformin, exercise, and diet on microvascular complication risk over time among T2D patients in the U.S. and Canada. Hypothesis: We hypothesize that the combined effects of metformin, exercise, and diet would be better than their individual effects on microvascular complication risk. Methods: We analyzed data from 923 participants [mean age: 62.6; 39.2% female; mean years with diabetes: 10.7] of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) (2003-2009) trial. Adequate exercise was defined as &gt; 150 mins of moderate-intensity physical activity per week. Metformin use was defined as yes vs. no. An adequate diet score was ≤ 2.4 of the summary fat intake score (range: 0 - 5). We defined composite outcomes for microvascular complications (i.e., nephropathy, retinopathy, and neuropathy) based on several measurements including serum creatinine doubling, decrease in estimated glomerular filtration ratio (≥ 20 ml/min/1.73 m2 decrease), vision loss, Michigan Neuropathy Screening Instrument. We performed longitudinal analysis with synergy factor (SF) approach using multinomial logistic regression models adjusted for sex, diabetes years, education, alcohol, treatment arm, and baseline outcome. Results: Among individuals with poor diet score, those taking metformin but not adequate exercise had an odds ratio of 1.12 (95% CI: 0.65 - 1.94, p = 0.68) for microvascular complication. Those not taking metformin but had adequate exercise had an odds ratio of 2.71 (95% CI: 1.12 - 6.59, p &lt; 0.05). However, taking metformin and having adequate exercise produced an odds ratio of 0.90 (95% CI: 0.49 - 1.67, p = 0.75), which was 0.30 times less than the predicted odds of the joint effect (SF = 0·30, 95% CI: 0 - 0.59, p = 0·05). Individuals with an adequate diet, adequate exercise, and taking metformin had an odds ratio of 0.85 (95% CI: 0.48 - 1.49, p = 0.57). However, we did not find these associations to be statistically significant. A similar pattern holds for individual microvascular complication outcomes. Conclusion: Additional randomized controlled trials are needed to confirm the potential additive beneficial effect of metformin, adequate exercise, and adequate diet combination over their individual effects on odds of microvascular complications.

Trajectories of Body Mass Index and Risk for Diabetes Complications and All-Cause Mortality in Finnish Type 2 Diabetes Patients.

We aimed to assess how longitudinal body mass index (BMI) trajectories are associated with diabetes complications and all-cause mortality in Finnish patients with type 2 diabetes (T2D). In this cohort study, electronic health records from public primary and specialized healthcare services in all 13 municipalities of North Karelia, Finland, were utilized. This study included a total of 889 adults with newly diagnosed T2D in 2011 or 2012 (mean age at baseline 62.0 years). Individual BMI trajectories from the T2D diagnosis until 2014 were estimated and grouped by growth mixture modeling (GMM). Hazard ratios (HRs) with 95% confidence intervals (CIs) for microvascular complications, macrovascular complications, any diabetes complications, and all-cause mortality from 2015 to 2022 across BMI trajectory groups were estimated using Cox regression models. Three distinct BMI trajectory groups were identified using GMM and labeled as follows: "stable" (n = 774, 87.1%), "decreasing" (n = 87, 9.8%), and "increasing" (n = 28, 3.1%). During a median follow-up of 8 years, there were 119 (13.3%) patients with microvascular complications, 187 (21.0%) with macrovascular complications, 258 (29.0%) with any diabetes complications, and 180 (20.2%) deaths. Compared with the "stable" BMI, the "increasing" BMI was associated with an increased risk of microvascular complications (HR = 2.88, 95% CI: 1.32 to 6.28), macrovascular complications (HR = 2.52, 95% CI: 1.17 to 5.43), and any diabetes complications (HR = 2.21, 95% CI: 1.16 to 4.20). The "decreasing" BMI was associated with an increased risk of all-cause mortality (HR = 1.90, 95% CI: 1.14 to 3.15), compared to the "stable" BMI. Our findings underscore the significance of continuous BMI monitoring and weight management in patients with T2D. Tailored treatments are crucial for efficiently preventing weight gain and reducing the risk of diabetes complications.

Lipid variability and risk of microvascular complications in patients with diabetes: a systematic review and meta-analysis

Background and aimsThe current systematic review aimed to elucidate the effects of lipid variability on microvascular complication risk in diabetic patients. The lipid components studied were as follows: High-density lipoprotein (HDL), High-density lipoprotein (LDL), Triglyceride (TG), Total Cholesterol (TC), and Remnant Cholesterol (RC).MethodWe carried out a systematic search in multiple databases, including PubMed, Web of Science, and SCOPUS, up to October 2nd, 2023. After omitting the duplicates, we screened the title and abstract of the studies. Next, we retrieved and reviewed the full text of the remaining articles and included the ones that met our inclusion criteria in the study.ResultIn this research, we examined seven studies, comprising six cohort studies and one cross-sectional study. This research was conducted in Hong Kong, China, Japan, Taiwan, Finland, and Italy. The publication years of these articles ranged from 2012 to 2022, and the duration of each study ranged from 5 to 14.3 years. The study group consisted of patients with type 2 diabetes aged between 45 and 84 years, with a diabetes history of 7 to 12 years. These studies have demonstrated that higher levels of LDL, HDL, and TG variability can have adverse effects on microvascular complications, especially nephropathy and neuropathic complications. TG and LDL variability were associated with the development of albuminuria and GFR decline.Additionally, reducing HDL levels showed a protective effect against microalbuminuria. However, other studies did not reveal an apparent relationship between lipid variations and microvascular complications, such as retinopathy. Current research lacks geographic and demographic diversity. Increased HDL, TG, and RC variability have been associated with several microvascular difficulties. Still, the pathogenic mechanism is not entirely known, and understanding how lipid variability affects microvascular disorders may lead to novel treatments. Furthermore, the current body of this research is restricted in its coverage. This field's lack of thorough investigations required a more extensive study and comprehensive effort.ConclusionThe relationship between lipid variation (LDL, HDL, and TG) (adverse effects) on microvascular complications, especially nephropathy and neuropathic (and maybe not retinopathy), is proven. Physicians and health policymakers should be highly vigilant to lipid variation in a general population.