United Kingdom Prospective Diabetes Study Research Articles

Current type 2 diabetes guidelines: Individualized treatment and how to make the most of metformin.

Evidence-based guidelines provide the premise for the delivery of quality care to preserve health and prevent disabilities and premature death. The systematic gathering of observational, mechanistic and experimental data contributes to the hierarchy of evidence used to guide clinical practice. In the field of diabetes, metformin was discovered more than 100 years ago, and with 60 years of clinical use, it has stood the test of time regarding its value in the prevention and management of type 2 diabetes. Although some guidelines have challenged the role of metformin as the first-line glucose-lowering drug, it is important to point out that the cardiovascular-renal protective effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were gathered from patients with type 2 diabetes, the majority of whom were treated with metformin. Most national, regional and international guidelines recommend metformin as a foundation therapy with emphasis on avoidance of therapeutic inertia and early attainment of multiple treatment goals. Moreover, real-world evidence has confirmed the glucose-lowering and cardiovascular-renal benefits of metformin accompanied by an extremely low risk of lactic acidosis. In patients with type 2 diabetes and advanced chronic kidney disease (estimated glomerular filtration rate 15-30 mL/min/1.73m2), metformin discontinuation was associated with an increased risk of cardiovascular-renal events compared with metformin persistence. Meanwhile, it is understood that microbiota, nutrients and metformin can interact through the gut-brain-kidney axis to modulate homeostasis of bioactive molecules, systemic inflammation and energy metabolism. While these biological changes contribute to the multisystem effects of metformin, they may also explain the gastrointestinal side effects and vitamin B12 deficiency associated with metformin intolerance. By understanding the interactions between metformin, foods and microbiota, healthcare professionals are in a better position to optimize the use of metformin and mitigate potential side effects. The United Kingdom Prospective Diabetes Study and the Da Qing Diabetes Prevention Program commenced 40 years ago provided the first evidence that type 2 diabetes is preventable and treatable. To drive real-world impact fromthis evidence, payors, practitioners and planners need to co-design and implement an integrated, data-driven, metformin-based programme to detect people with undiagnosed diabetes and prediabetes (intermediate hyperglycaemia), notably impaired glucose tolerance, for early intervention. The systematic data collection will create real-world evidence to bring out the best of metformin and make healthcare sustainable, affordable and accessible.

Estimating Risk Factor Time Paths Among People with Type 2 Diabetes and QALY Gains from Risk Factor Management.

Most type 2 diabetes simulation models utilise equations mapping out lifetime trajectories of risk factors [e.g. glycated haemoglobin (HbA1c)]. Existing equations, using historic data or assuming constant risk factors, frequently underestimate or overestimate complication rates. Updated risk factor time path equations are needed for simulation models to more accurately predict complication rates. (1) Update United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2) risk factor time path equations; (2) compare quality-adjusted life-years (QALYs) using original and updated equations; and (3) compare QALY gains for reference case simulations using different risk factor equations. Using pooled contemporary data from two randomised trials EXSCEL and TECOS (n = 28,608), we estimated: dynamic panel models of seven continuous risk factors (high-density lipoprotein cholesterol, low density lipoprotein cholesterol, HbA1c, haemoglobin, heart rate, blood pressure and body mass index); two-step models of estimated glomerular filtration rate; and survival analyses of peripheral arterial disease, atrial fibrillation and albuminuria. UKPDS-OM2-derived lifetime QALYs were extrapolated over 70 years using historical and the new risk factor equations. All new risk factor equation predictions were within 95% confidence intervals of observed values, displaying good agreement between observed and estimated values. Historical risk factor time path equations predicted trial participants would accrue 9.84 QALYs, increasing to 10.98 QALYs using contemporary equations. Incorporating updated risk factor time path equations into diabetes simulation models could give more accurate predictions of long-term health, costs, QALYs and cost-effectiveness estimates, as well as a more precise understanding of the impact of diabetes on patients' health, expenditure and quality of life. ClinicalTrials.gov NCT01144338 and NCT00790205.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study

BackgroundThe residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.MethodsData on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.ResultsThe 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.ConclusionThis study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights.

Metformin is an orally effective anti-hyperglycemic drug that despite being introduced over 60 years ago is still utilized by an estimated 120 to 150 million people worldwide for the treatment of type 2 diabetes (T2D). Metformin is used off-label for the treatment of polycystic ovary syndrome (PCOS) and for pre-diabetes and weight loss. Metformin is a safe, inexpensive drug with side effects mostly limited to gastrointestinal issues. Prospective clinical data from the United Kingdom Prospective Diabetes Study (UKPDS), completed in 1998, demonstrated that metformin not only has excellent therapeutic efficacy as an anti-diabetes drug but also that good glycemic control reduced the risk of micro- and macro-vascular complications, especially in obese patients and thereby reduced the risk of diabetes-associated cardiovascular disease (CVD). Based on a long history of clinical use and an excellent safety record metformin has been investigated to be repurposed for numerous other diseases including as an anti-aging agent, Alzheimer's disease and other dementias, cancer, COVID-19 and also atrial fibrillation (AF). AF is the most frequently diagnosed cardiac arrythmia and its prevalence is increasing globally as the population ages. The argument for repurposing metformin for AF is based on a combination of retrospective clinical data and in vivo and in vitro pre-clinical laboratory studies. In this review, we critically evaluate the evidence that metformin has cardioprotective actions and assess whether the clinical and pre-clinical evidence support the use of metformin to reduce the risk and treat AF.

A health economic analysis of an integrated diabetes care program in China: based on real-world evidence.

An integrated care program was set up in China to improve the collaboration between primary healthcare centers and hospitals on diabetes management. This study aims to evaluate the economic value of this program with real-world data and to examine whether it can be promoted in primary healthcare settings in China. This integrated diabetes care program was implemented in Yuhuan City, China, to coordinate primary care and specialty care, treatment and prevention services, as well as the responsibilities of doctors and nurses. Cost-effectiveness analysis was used to compare the short-term economic value of this program (intervention group) versus usual diabetes management (control group). The cost data were collected from a societal perspective, while the effectiveness indicators pointed to the improvement of control rates of fasting blood glucose (FBG), systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels after the 1 year intervention. In addition, cost-utility analysis was applied to evaluate the long-term value of the two groups. Patients' long-term diabetes management costs and quality-adjusted life years (QALYs) were simulated by the United Kingdom Prospective Diabetes Study Outcomes Model 2. The results showed that for 1% FBG, SPB, and DBP control rate improvement, the costs for the intervention group were 290.53, 124.39, and 249.15 Chinese Yuan (CNY), respectively, while the corresponding costs for the control group were 655.19, 610.43, and 1460.25 CNY. Thus, the intervention group's cost-effectiveness ratios were lower than those of the control group. In addition, compared to the control group, the intervention group's incremental costs per QALY improvement were 102.67 thousand CNY, which means that the intervention was cost-effective according to the World Health Organization's standards. In conclusion, this study suggested that this integrated diabetes care program created short-term and long-term economic values through patient self-management support, primary care strengthening, and care coordination. As this program followed the principles of integrated care reform, it can be promoted in China. Also, its elements can provide valuable experience for other researchers to build customized integrated care models.

Repurposing Metformin for Vascular Disease.

Metformin has been used as an oral anti-hyperglycaemic drug since the late 1950s; however, following the release in 1998 of the findings of the 20-year United Kingdom Prospective Diabetes Study (UKPDS), metformin use rapidly increased and today is the first-choice anti-hyperglycaemic drug for patients with type 2 diabetes (T2D). Metformin is in daily use by an estimated 150 million people worldwide. Historically, the benefits of metformin as an anti-diabetic and cardiovascular-protective drug have been linked to effects in the liver, where it acts to inhibit gluconeogenesis and lipogenesis, as well as reduce insulin resistance and enhance peripheral glucose utilization. However, direct protective effects on the endothelium and effects in the gut prior to metformin absorption are now recognized as important. In the gut, metformin modulates the glucagon-like peptide- 1 (GLP-1) - gut-brain axis and impacts the intestinal microbiota. As the apparent number of putative tissue and cellular targets for metformin has increased, so has the interest in re-purposing metformin to treat other diseases that include polycystic ovary syndrome (PCOS), cancer, neurodegenerative diseases, and COVID-19. Metformin is also being investigated as an anti-ageing drug. Of particular interest is whether metformin provides the same level of vascular protection in individuals other than those with T2D, including obese individuals with metabolic syndrome, or in the setting of vascular thromboinflammation caused by SARS-CoV-2. In this review, we critically evaluate the literature to highlight clinical settings in which metformin might be therapeutically repurposed for the prevention and treatment of vascular disease.

Cost-effectiveness analysis of once-daily oral semaglutide versus placebo and subcutaneous glucagon-like peptide-1 receptor agonists added to insulin in patients with type 2 diabetes in China.

Introduction: Oral semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that improves glycated hemoglobin levels and body weight in patients with type 2 diabetes (T2DM). We aim to evaluate the cost-effectiveness of once-daily oral semaglutide in comparison to placebo and injectable GLP-1 RAs in Chinese patients with T2DM inadequately controlled on basal insulin. Methods: The United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS OM2.1) was used to estimate the cost-effectiveness by calculating the incremental cost-effectiveness ratio (ICER). Baseline characteristics of the simulation cohort were obtained from the PIONEER 8 trial. Utility and safety inputs were derived from a network meta-analysis of 12 trials. Direct medical costs were retrieved from published literature and discounted at an annual rate of 5%. We used a willingness-to-pay (WTP) threshold of $36,528.3 per quality-adjusted life-year (QALY) gained. Scenario analysis, and one-way and probabilistic sensitivity analysis were performed. Results: The effectiveness of oral semaglutide was 10.39 QALYs with a total cost of $30,223.10, while placebo provided 10.13 QALYs at a lower total cost of $20,039.19. Oral semaglutide was not cost-effective at an ICER of $39,853.22 and $88,776.61 per QALY compared to placebo and exenatide at the WTP. However, at an annual price of $1,871.9, it was cost-effective compared with dulaglutide, liraglutide, and lixisenatide. The model was most sensitive to the discount rate and annual cost of oral semaglutide. The price of oral semaglutide needed to be reduced to $1,711.03 per year to be cost-effective compared to placebo and other injectable GLP-1 RAs except for exenatide and semaglutide injection. Conclusion: We found that once-daily oral semaglutide, at a comparable price of semaglutide injection, proves to be a cost-effective add-on therapy to insulin for Chinese patients with T2DM, especially when compared to subcutaneous GLP-1 RAs other than injectable semaglutide and exenatide. However, to achieve cost-effectiveness in comparison to placebo, further cost reduction of oral semaglutide is necessary. The estimated annual cost of $1,711.03 for oral semaglutide demonstrates a more cost-effective option than placebo, highlighting its potential value in the management of T2DM.

Endocan is Related to Increased Cardiovascular Risk in Type 2 Diabetes Mellitus Patients.

Aim: Type 2 diabetes mellitus (T2D) patients have an increased risk for cardiovascular disease (CVD). Different algorithms are used for the CVD risk quantification and United Kingdom Prospective Diabetes Study (UKPDS) score was among the most validated. Endocan is a novel endothelial dysfunction marker. The aim was to explore the potential relationship between serum endocan level and UKPDS risk engine score [which enables calculation of the 10-year risk of nonfatal and fatal coronary heart disease (eCHD) and stroke] in T2D patients. Materials and Methods: The study included a cohort of 104 patients with T2D (of them 52.8% men), with median age 66 years and body mass index (BMI) = 30.7 kg/m2. Patients were divided into: low (<15%), moderate (≥15% and <30%), and high-risk UKPDS category (≥30%). Results: In multivariable regression analysis (when adjusted for sex, BMI and/or hip circumference), endocan was the independent predictor for moderate and high estimated risks (nonfatal eCHD, fatal eCHD, and nonfatal stroke risk). In the Model for high nonfatal eCHD [areas under curve (AUC) = 0.895] and high fatal eCHD (AUC = 0.860) endocan indicated good clinical accuracy, and an excellent accuracy in discriminating patients with high risk for nonfatal stroke risk (AUC = 0.945). Conclusion: Endocan was the independent predictor for moderate and high estimated risks (i.e., nonfatal and fatal CHD and nonfatal stroke risk scores) in T2D patients. When included in models with sex and obesity indices endocan demonstrated good clinical accuracy in discriminating T2D patients with high risk for nonfatal and fatal eCHD and nonfatal stroke risk from those patients with low risk.

Valor pronóstico a 10 años de la angiografía coronaria por TAC en pacientes asintomáticos con diabetes tipo 2

Introduction and objectivesThe United Kingdom Prospective Diabetes Study (UKPDS) risk score has limited value for predicting coronary artery disease (CAD) events. We investigated the additive value of coronary computed tomography angiography (CCTA) on top of the UKPDS risk score in predicting 10-year adverse cardiac events in asymptomatic patients with type 2 diabetes. MethodsWe evaluated 589 asymptomatic diabetic patients without a history of CAD who underwent CCTA. The primary outcome was a composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and revascularization. We estimated the discrimination and reclassification ability for the prediction models, which included combinations of the UKPDS category, severity of stenosis, and coronary artery calcium score by CCTA. ResultsThe incidence of the primary outcome was 12.4%. During 10 years of follow-up, patients without plaque by CCTA tended to have a low CAD event rate, while those with obstructive CAD tended to have a high event rate, irrespective of the baseline UKPDS risk category. The model that included only the UKPDS category had a Harrell's c-index of 0.658; adding the degree of stenosis to the model significantly increased the c-index by 0.066 (P=.004), while adding coronary artery calcium score increased the c-index by only 0.039 (P=.056). Overall, CCTA information in addition to the UKPDS risk category improved the reclassification rate for predicting the primary outcome. ConclusionsIn asymptomatic patients with type 2 diabetes, CCTA information for CAD provided significant incremental discriminatory power beyond the UKPDS risk score category for predicting 10-year adverse coronary events.

Ten-year prognostic value of coronary CT angiography in asymptomatic patients with type 2 diabetes

Introduction and objectivesThe United Kingdom Prospective Diabetes Study (UKPDS) risk score has limited value for predicting coronary artery disease (CAD) events. We investigated the additive value of coronary computed tomography angiography (CCTA) on top of the UKPDS risk score in predicting 10-year adverse cardiac events in asymptomatic patients with type 2 diabetes. MethodsWe evaluated 589 asymptomatic diabetic patients without a history of CAD who underwent CCTA. The primary outcome was a composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and revascularization. We estimated the discrimination and reclassification ability for the prediction models, which included combinations of the UKPDS category, severity of stenosis, and coronary artery calcium score by CCTA. ResultsThe incidence of the primary outcome was 12.4%. During 10 years of follow-up, patients without plaque by CCTA tended to have a low CAD event rate, while those with obstructive CAD tended to have a high event rate, irrespective of the baseline UKPDS risk category. The model that included only the UKPDS category had a Harrell's c-index of 0.658; adding the degree of stenosis to the model significantly increased the c-index by 0.066 (P=.004), while adding coronary artery calcium score increased the c-index by only 0.039 (P=.056). Overall, CCTA information in addition to the UKPDS risk category improved the reclassification rate for predicting the primary outcome. ConclusionsIn asymptomatic patients with type 2 diabetes, CCTA information for CAD provided significant incremental discriminatory power beyond the UKPDS risk score category for predicting 10-year adverse coronary events.

EE137 Evaluating the Effects of the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model Risk Factor Progression Equations on Cost-Utility Outcomes in Type 2 Diabetes: Analyses Using the Prime Diabetes Model

The United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS OM) and the risk equations that drive it remain widely used in the economic modeling of type 2 diabetes mellitus. Two versions of the UKPDS OM have been developed and published to-date (OM1 and OM2). The UKPDS OM2 was based on substantially longer follow-up, was derived from more events, and captured more complications and covariates than UKPDS OM1. The objective was to evaluate differences in the performance of the OM1 and OM2 risk factor trajectory equations for glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) in economic evaluations.

Role of insulin signaling and its associated signaling in glomerulus for diabetic kidney disease.

The number of patients with diabetic kidney disease (DKD) has been rising significantly over the last several decades and is one of the most frequent causes of chronic kidney disease (CKD) in the United States. Hyperglycemia accelerates development of DKD, a direct result of increased intracellular glucose availability. Two large clinical studies, the Diabetes Control and Complications Trial in type 1 diabetes and the United Kingdom Prospective Diabetes Study in type 2 diabetes showed that intensive glycemic control delayed the onset and the progression of DKD. On the other hand, it is reported that glycemic control alone is not sufficient to control DKD progression. Recent data support that insulin signaling and its associated signaling contribute significantly to preserve glomerular function. However, little is known about the key regulators of insulin signaling in glomerular component cells. In this review, we summarize the novel knowledge regarding the reno-protective effects of insulin signaling or its associated signaling in glomerular constituent cells on DKD.

Health and economic effects on patients with type 2 diabetes mellitus in the long run: predictions for the Chilean population

BackgroundDiabetes is associated to a high financial and disease burden, explaining a large proportion of expenditure of the health system in one year. The purpose of this study was to estimate long-term costs and health outcomes of recently diagnosed patients with type 2 diabetes in Chile.MethodsCost and consequence study based on mathematical discrete event simulation (DES) model. We modelled expected costs (USD) and quality-adjusted life-years (QALYs) from diagnosis to death (or the age of 95) of a hypothetical cohort of 100,000 incident cases, simulated based on the Chilean National Health Survey 2018. The incidence of twelve complications was estimated assuming the hazard functions provided by the United Kingdom Prospective Diabetes Study. We explore heterogeneity across patients based on their baseline risk covariates and their impact on costs and QALYs.ResultsThe expected cost and QALY of a recently diagnosed type 2 diabetes patient in Chile were USD 8660 and 12.44 QALYs. Both costs and QALYs were independently determined by baseline risk and the patient's life expectancy from the diagnosis. Length of life since diagnosis showed the major impact on costs (5.2% increase for every additional year). Myocardial infarction was the most frequent complication (47.4%) and the most frequent cause of death.ConclusionDiabetes type 2 determines a significant expenditure of the health system and substantial health losses. Although the control of cardiovascular risk factors and the metabolic control of the disease, both have an important impact on costs and outcomes, the main impact is achieved by postponing the age of onset of the disease.

Cost-utility analysis of semaglutide for type 2 diabetes after its addition to the National Medical Insurance System in China.

The main research purpose is to compare the long-term cost-effectiveness of semaglutide (SEMA) with that of dulaglutide (DULA) for patients with inadequately controlled type 2 diabetes throughout their lifetime. If necessary, the second aim is to investigate a further price cut for SEMA to provide sound advice for government drug price adjustments. Cost-utility analysis was performed by the United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS OM2) from the perspective of health care providers in China. Baseline characteristics and clinical efficacy of SEMA and DULA were sourced from the high-dose comparison in the SUSTAIN-7 trial. A binary search was used to identify the scope for further reduction in the price of SEMA. The impact of individual parameters was assessed with sensitivity analyses. Main analysis (SEMA vs. DULA) revealed a mean difference in quality-adjusted life years (QALYs) of 0.04 QALYs and costs of $1132.29. The incremental cost-utility ratio was $26 957.44/QALY, showing that SEMA was a better option compared with DULA. In sensitivity analyses, the discount rate made the greatest contribution to the incremental cost-utility ratio. In the binary search, there was still scope to reduce the SEMA cost further by approximately 6.83% to be cost-effective, taking DULA as a reference. After its addition to the National Medical Insurance System in China, SEMA is expected to be a cost-effective choice compared with DULA for patients with type 2 diabetes with inadequately controlled from the cost-utility analysis. However, there is still scope to reduce the annual cost of SEMA further.

A cross-talk between perceptions and reality on insulin therapy among Type-2 diabetes patients in developing countries

It has been reported that some healthcare providers in the developing countries may be unwilling to initiate insulin treatment due to multiple reasons including the patients’ resistance to accept insulin prescription [1]. World-wide, it is well established that optimal control of the blood glucose levels of type 2 diabetes patients constitute a major challenge for the patients as well as healthcare providers particularly for patients living in the developing countries [2]. The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated some decades ago that most type 2 diabetes patients had only 50 % of normal insulin secretion on diagnosis which decreases to 25 % after six years of diabetes duration [3].

Coronary computed tomography angiography as a screening tool for moderate-high risk asymptomatic type 2 diabetes mellitus patients.

BackgroundThere are few data on the clinical significance of coronary computed tomography angiography (CCTA) in asymptomatic type 2 diabetes mellitus (T2DM) patients. We performed a retrospective study to evaluate coronary heart disease (CHD) screening in asymptomatic patients with T2DM using CCTA and CHD risk stratification prediction.Materials and methodsData from 141 T2DM patients (58 ± 8 years, 57% males) without known symptoms suggestive of CHD who underwent CCTA were retrospectively analyzed. The patients were classified into three subgroups based on United Kingdom prospective diabetes study (UKPDS) CHD risk stratification prediction. Seventy-four patients without diabetes mellitus and CHD who underwent CCTA successively were chosen as the control group. The segment involvement score (SIS), segment stenosis score (SSS), stenosis coefficient (SC), severe proximal plaque (SPP) positive ratio and CCTA-adapted Leaman score (CT-LeSc) based on CCTA data were evaluated and compared among the groups.ResultsCompared with the patients in the control group, patients in the moderate-high risk DM groups had higher scores on the SIS, SSS, SC, CT-LeSc, and a higher SPP positive ratio (all p-values < 0.001), and no difference was observed between the low-risk group and the control group (p = 0.136, p = 0.088, p = 0.0.067, p = 0.225, p = 1.000, respectively). Compared with patients in the control group, the patients in the moderate-high risk DM groups had increased odds of SIS > 3 [odds ratio (OR) = 6.557, p < 0.001; OR = 4.455, p < 0.001, respectively], SSS > 5 (OR = 5.727, p < 0.001; OR = 5.144, p < 0.001, respectively), CT-LeSc > 8.7 (OR = 3.780, p = 0.001; OR = 2.804, p = 0.007, respectively), and obstructive stenosis (OR = 7.233, p < 0.001; OR = 5.787, p < 0.001, respectively).ConclusionThe moderate-high CHD risk patients had increased odds of obstructive coronary artery stenosis, and the distribution of coronary artery stenosis was more extensive and more severe in that group compared to the patients without diabetes mellitus and CHD. CHD can be effectively screened in moderate-high risk asymptomatic T2DM patients using CCTA.

Higher systemic inflammatory status and cardiovascular risk associated with Charcot arthropathy unrelated to infection or extremity amputation.

People with diabetes and Charcot arthropathy have higher mortality than people with diabetes without this complication. Are the causes of this higher mortality exclusively infectious or of a cardiovascular origin? We aimed to study aspects related to cardiovascular risk and inflammation in a population of people with type 2 diabetes with and without Charcot arthropathy. A cross-sectional study was performed in people with diabetes and Charcot Eickenholtz III arthropathy, matched for sex and age, with two groups of people with diabetes without Charcot arthropathy with and without peripheral sensory-motor neuropathy, in the absence of active infection. All participants underwent clinical and laboratory evaluation at the time of the interview, and their cardiovascular risk was calculated according to the United Kingdom Prospective Diabetes Study (UKPDS) calculator. We evaluated 69 people with type 2 diabetes (21 with Charcot arthropathy, 24 with diabetic peripheral neuropathy and 24 without this neuropathy), with a mean age between 57 and 61years and with a diabetes duration of more than 10years. Patients with Charcot arthropathy had a longer duration of diabetes; more frequency of dyslipidemia; and higher levels of uric acid, microalbuminuria and C-reactive protein than the other two groups. A total of 73.9% of the people evaluated had high or very high cardiovascular risk according to the UKPDS score. The people with type 2 diabetes presenting Charcot arthropathy had greater values of systemic inflammatory parameters, even in the chronic phase of the complication, with a higher risk of mortality unrelated to infections.

894-P: The Potential Value of Clustering-Based Type 2 Diabetes Subgroups for Guiding Intensive Treatment: A Maximum Cost-Based Comparison with Threshold-Based Classifications

Aim: To quantify and compare the performance of setting priority for intensive treatment by novel clustering-based subgroups to threshold-based classifications using systematic coronary risk evaluation (SCORE) and HbA1c levels. Methods: We divided 2,935 patients from the Hoorn diabetes care system cohort into five clustering-based subgroups: severe insulin-deficient (SIDD) , severe insulin-resistant (SIRD) , mild obesity-related (MOD) mild (MD) , and mild with high HDL-cholesterol (MDH) diabetes, and four risk threshold-based subgroups. The United Kingdom Prospective Diabetes Study Outcomes Model was used to simulate lifetime health outcomes in the U.S. and U.K. settings. Gains from hypothetical treatment scenarios based on clinical guidelines were compared to “care-as-usual” and expressed in incremental quality-adjusted life-expectancy (QALE) and complication costs. Results: The SIRD and MOD subgroup had the lowest absolute and age-sex-standardized QALE, respectively (7.90; 9.07) . Threshold-based classifications better discriminated between patients with higher and lower absolute and standardized QALE than clustering-based subgroups. For MOD, hypothetical interventions costing up to $1973 (95%CI $1444-$2603) and £463 (95%CI £345-£603) per year would be cost-effective at $100,000 and £20,000 per QALY thresholds in the U.S. and U.K., respectively. The MOD, SIDD and SIRD subgroups had the best potential cost-effectiveness alongside the subgroup with high HbA1c and high SCORE. Conclusions: Intensified treatment could be cost-effective at higher-than-average costs for three out of five of the clustering-based subgroups and two out of four of the threshold-based classifications. Both classification methods support priority setting for intensive treatment, but the threshold-based method may better identify those who have the most potential to benefit from intensified treatment. Disclosure X.Li: None. A.Van giessen: None. J.Altunkaya: None. R.Slieker: None. J.Beulens: None. E.Pearson: Speaker's Bureau; Sanofi. P.J.M.Elders: None. T.Feenstra: Research Support; Dutch Healthcare Institute (ZIN) , European Union/IMI Rhapsody. J.Leal: None. Funding RHAPSODY (115881)

Serum Homocysteine Level in Patients of Type 2 Diabetes Mellitus with Macrovascular Complications

The risk of CVD in men with DM is 3-fold and in women with DM 5-fold in comparison to those without diabetes(1). Diabetes is a recognized independent risk factor for stroke and is associated with higher morbidity and mortality(2-4). The severity and duration of DM are important predictors of both the incidence and the extent of PAD, as observed in United Kingdom Prospective Diabetes Study, where each 1% increase in glycosylated hemoglobin was correlated with a 28% increase in incidence of PAD, and higher rates of death, microvascular complications and major amputation.(5,6) Homocysteine concentration is found to be higher in patients with peripheral vascular, cerebrovascular and coronary artery diseases than those without such diseases.(7) This observational comparative study was done at Ramakrishna Care Hospital, Raipur, from January 2017 to June 2018 involving 100 type 2 diabetes mellitus patients. Patients were divided into two groups- Group 1: The Case Group- Type 2 DM patients with macrovascular complications. Group 2: The Control Group - Type 2 DM patients without any macrovascular complications With the help of Clinical evaluation and detailed investigations we had determined the presence of macrovascular complications in which we had included Myocardial infarction, CVA and Peripheral vascular disease. Data obtained from these patients were analysed and the results were compared with prior studies of similar objectives. Higher age and duration of diabetes thus had a positive correlation with macrovascular disease. The mean serum homocysteine level was statistically significant and they correlate with higher incidence of macrovascular disease in males and with increasing age. Keywords: Type 2 Diabetes Mellitus, DM, CVD, CVA, Serum Homocysteine Level, Macrovascular Complications.

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.