Diagnosis of infection in the foot of patients with diabetes: A systematic review.

BACKGROUND: Securing an early accurate diagnosis of diabetic foot infections and assessment of their severity are of paramount importance since these infections can cause great morbidity and potential mortality and present formidable challenges in surgical and antimicrobial treatment. METHODS: In June 2022, we searched the literature using PubMed and EMBASE for published studies on the diagnosis of diabetic foot infection (DFI). On the basis of pre-determined criteria, we reviewed prospective controlled, as well as non-controlled, studies in English. We then developed evidence statements based on the included papers. RESULTS: We selected a total of 64 papers that met our inclusion criteria. The certainty of the majority of the evidence statements was low because of the weak methodology of nearly all of the studies. The available data suggest that diagnosing diabetic foot infections on the basis of clinical signs and symptoms and classified according to the International Working Group of the Diabetic Foot/Infectious Diseases Society of America scheme correlates with the patient's likelihood of the need for hospitalisation, lower extremity amputation, and risk of death. Elevated levels of selected serum inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein and procalcitonin are supportive, but not diagnostic, of soft tissue infection. Culturing tissue samples of soft tissues or bone, when care is taken to avoid contamination, provides more accurate microbiological information than culturing superficial (swab) samples. Although non-culture techniques, especially next-generation sequencing, are likely to identify more bacteria from tissue samples including bone than standard cultures, no studies have established a significant impact on the management of patients with DFIs. In patients with suspected diabetic foot osteomyelitis, the combination of a positive probe-to-bone test and elevated ESR supports this diagnosis. Plain X-ray remains the first-line imaging examination when there is suspicion of diabetic foot osteomyelitis (DFO), but advanced imaging methods including magnetic resonance imaging (MRI) and nuclear imaging when MRI is not feasible help in cases when either the diagnosis or the localisation of infection is uncertain. Intra-operative or non-per-wound percutaneous biopsy is the best method to accurately identify bone pathogens in case of a suspicion of a DFO. Bedside percutaneous biopsies are effective and safe and are an option to obtain bone culture data when conventional (i.e. surgical or radiological) procedures are not feasible. CONCLUSIONS: The results of this systematic review of the diagnosis of diabetic foot infections provide some guidance for clinicians, but there is still a need for more prospective controlled studies of high quality.

IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections (IWGDF/IDSA 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

Interventions in the management of diabetes-related foot infections: A systematic review.

The optimal approaches to managing diabetic foot infections remain a challenge for clinicians. Despite an exponential rise in publications investigating different treatment strategies, the various agents studied generally produce comparable results, and high-quality data are scarce. In this systematic review, we searched the medical literature using the PubMed and Embase databases for published studies on the treatment of diabetic foot infections from 30 June 2018 to 30 June 2022. We combined this search with our previous literature search of a systematic review performed in 2020, in which the infection committee of the International Working Group on the Diabetic Foot searched the literature until June 2018. We defined the context of the literature by formulating clinical questions of interest, then developing structured clinical questions (Patients-Intervention-Control-Outcomes) to address these. We only included data from controlled studies of an intervention to prevent or cure a diabetic foot infection. Two independent reviewers selected articles for inclusion and then assessed their relevant outcomes and methodological quality. Our literature search identified a total of 5,418 articles, of which we selected 32 for full-text review. Overall, the newly available studies we identified since 2018 do not significantly modify the body of the 2020 statements for the interventions in the management of diabetes-related foot infections. The recent data confirm that outcomes in patients treated with the different antibiotic regimens for both skin and soft tissue infection and osteomyelitis of the diabetes-related foot are broadly equivalent across studies, with a few exceptions (tigecycline not non-inferior to ertapenem [±vancomycin]). The newly available data suggest that antibiotic therapy following surgical debridement for moderate or severe infections could be reduced to 10 days and to 3 weeks for osteomyelitis following surgical debridement of bone. Similar outcomes were reported in studies comparing primarily surgical and predominantly antibiotic treatment strategies in selected patients with diabetic foot osteomyelitis. There is insufficient high-quality evidence to assess the effect of various recent adjunctive therapies, such as cold plasma for infected foot ulcers and bioactive glass for osteomyelitis. Our updated systematic review confirms a trend to a better quality of the most recent trials and the need for further well-designed trials to produce higher quality evidence to underpin our recommendations.

IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections (IWGDF/IDSA 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

[Innovation Stimulates Development: How to Cope with the Constant Growth in Refractory Diabetic Foot Ulcers].

Diabetic foot ulcers, with an annual incidence as high as 8.1% in China, impose enormous social and economic burdens on diabetic patients, families and society. Substantial progress has been made in China in the work concerning diabetic foot ulcers in the past two decades, and the major amputation rate in patients with diabetic foot ulcers in China has decreased significantly, even though it is still far higher than the level of developed countries in Europe and North America. Therefore, if we are to further improve the diagnosis and treatment of diabetic foot ulcers in China, the only solution lies in reinforced efforts in innovation, including innovations in concepts, models, and technology, and the training of national and provincial-level leading experts in diabetic foot ulcer care. Only in this way, can we further reduce the disability and mortality caused by diabetic foot ulcers in China. We, herein, discussed the importance and necessity of establishing a comprehensive diabetic foot prevention and control system suited to the actual circumstances of China through strengthening innovative research. On that basis, we also reported existing problems and prospects for future development.

Ertapenem versus piperacillin/tazobactam for diabetic foot infections in China: a Phase 3, multicentre, randomized, double-blind, active-controlled, non-inferiority trial.

OBJECTIVES: Few randomized controlled studies have compared antibiotic regimens against diabetic foot infections (DFIs) in Chinese patients. We evaluated the efficacy and safety of ertapenem versus piperacillin/tazobactam for the treatment of DFIs in Chinese patients. METHODS: Patients with moderate to severe DFIs requiring parenteral antibiotics were randomized in a 1 : 1 ratio to receive ertapenem (1.0 g once daily) or piperacillin/tazobactam (4.5 g every 8 h) by 30 min intravenous (iv) infusions for ≥5 days. The primary outcome was favourable clinical response at discontinuation of iv therapy (DCIV). An evaluable-patient population was identified for primary analysis of non-inferiority at -15%. Safety was assessed. ClinicalTrials.gov: NCT01370616. RESULTS: Of 565 patients randomized, 443 patients (ertapenem = 219 and piperacillin/tazobactam = 224) were clinically evaluable for primary analysis. In the clinically evaluable population, the proportions of patients with favourable clinical response at DCIV were 93.6% (205/219) and 97.3% (218/224) in the ertapenem and piperacillin/tazobactam groups, respectively (difference: -3.8%, 95% CI: -8.3%, 0.0%). Ertapenem had a significantly lower favourable clinical response rate (91.5% versus 97.2%, 95% CI for difference: -12.1%, -0.3%) at DCIV in severe DFI patients. In the modified ITT population, 88.8% (237/267) and 90.6% (241/266) of patients in the ertapenem and piperacillin/tazobactam groups, respectively, had favourable clinical responses at DCIV (difference: -1.9%, 95% CI: -7.3%, 3.3%). Microbiological eradications of causative pathogens and adverse events were similar between treatment groups. CONCLUSIONS: Treatment with ertapenem was non-inferior to piperacillin/tazobactam in Chinese patients with DFIs. Ertapenem treatment resulted in a markedly lower rate of clinical resolution in severe DFIs.

A cohort study of diabetic patients and diabetic foot ulceration patients in China.

To determine the annual incidence and clinically relevant risk factors for foot ulceration in a large cohort study of diabetic foot ulcer (DFU) patients and diabetes mellitus (DM) patients in China. To investigate a cohort of 1,333 patients comprising 452 DFU patients and 881 DM patients, who underwent foot screening, physical examination, and laboratory tests in eight hospitals. The patients were assessed at baseline in terms of their demographic information, medical and social history, peripheral neuropathy disease (PND) screening, periphery artery disease (PAD) screening, assessment of nutritional status, and diabetic control. One year later, the patients were followed up to determine the incidence of new foot ulcers, amputation, and mortality. By univariate analysis, statistically significant differences were found in age, location, gender, living alone (yes/no), occupation, smoking, hypertension, PND, PAD, nephropathy, retinopathy, cataracts, duration of diabetes, Glycosylated hemoglobin A (HbA1c), fasting plasma glucose level, postprandial blood glucose level, insulin level, blood urea nitrogen, creatinine, cholesterol, triglyeride, high density lipoprotein (HDL), serum albumin, white blood cell, and body mass index. A binary logistic regression model was used to examine which of these risk factors were independent risk factors for foot ulceration. A total of 687 (51.5%) of the 1,333 patients were followed up for an average of 12 months; there were 458 DM patients and 229 DFU patients. A total of 46 patients died during the follow-up period; 13 were DM patients, and 33 were DFU patients. Of the 641 patients, 445 (69.4%) patients were DM patients, and 196 (30.6%) were DFU patients. At follow-up, 36/445 DM patients (8.1%), and 62/196 DFU patients (31.6%), developed new ulcers; 10/196 DFU patients underwent an amputation. The annual incidence of ulceration for DM patients and amputation for DFU patients were 8.1 and 5.1%, respectively. The annual mortality of the DM patients and DMF patients were 2.8 and 14.4%, respectively. A binary logistic regression model was used to examine which risk factors were independent risk factors for foot ulceration during the follow-up period, and the final results showed that nephropathy (odds ratio 2.32), insulin level (odds ratio 3.136, 2.629), and decreased HDL (odds ratio 0.427) were associated with increased risks for foot ulceration. Complications of diabetes affecting the feet represent a serious problem in China. The incidence of foot ulcers and amputation are much higher than that of Western countries. More intensive surveillance and aggressive care following a diagnosis of DFU and earlier referral to specialty care might improve the patient outcome.

Glycemic control rate of T2DM outpatients in China: a multi-center survey.

BACKGROUND: Type 2 diabetes mellitus (T2DM)-associated mortality and morbidity are strongly dependent on glycemic control. With T2DM prevalence increasing in China, we aimed to assess glycemic control rates in Chinese T2DM outpatients. MATERIAL/METHODS: A total of 9065 adult T2DM outpatients (5035 men) were assessed in 26 Chinese medical centers between August 2010 and April 2012. Patients were stratified according to BMI (kg/m2): <24, 24-28, and >28. Successful glycemic control was defined as glycated hemoglobin A1c (HbA1c) ≤7% or fasting plasma glucose (FPG) <7.0 mmol/L. RESULTS: Among the participants included in this study, 2939 had BMI <24, 3361 had BMI of 24-28, and 2764 had BMI >28. The glycemic control rate was only 32.6%, and the triple control rate for glycemia, blood pressure, and lipidemia was only 11.2%. Glycemic control rates by BMI group were 33.7% (<24), 33.8% (24-28), and 30.2% (>28) (p=0.005), and corresponding incidences of cardiovascular diseases (CVD) were 12.2%, 15.7%, and 15.9% (p<0.001). Multivariate logistic regression analysis demonstrated that older age (p<0.001), higher BMI (p=0.026), larger waist circumference (p<0.001), less education (p<0.001), and recent diagnosis (p<0.001) were independent risk factors for poor glycemic control. CONCLUSIONS: The T2DM glycemic control rate in China is currently low, especially in older obese patients with poor education and recent diagnosis.

Trends in metabolic indicators and microvascular complications in Chinese adults with newly diagnosed type 2 diabetes: A retrospective, single-centre study of twenty-years.

BACKGROUND: The purpose of this study is to assess metabolic indicators and trends in microvascular complications among Chinese adults with newly diagnosed type 2 diabetes during 2000-2020. METHODS: 3,907 patients were included and divided into three groups according to a time period of 7 years. This study analyzed trends in proportions of patients reached therapeutic targets of blood glucose, pressure and lipids, and trends in albuminuria, retinopathy, and peripheral neuropathy. RESULTS: In the past 20 years, the age of adults with newly diagnosed type 2 diabetes tended to be younger, and the proportion of female patients increased. There seemed no improvements in blood glucose and pressure. The rate of awareness and treatment on target of hypertension was less than 50%. There was a significant decrease in the prevalence of retinopathy, but no changes in nephropathy or peripheral neuropathy. Complications were more common for patients who were smoker, male, or with hypertension and obesity. CONCLUSIONS: Over the past two decades, there have been encouraging reductions in retinopathy in Chinese adults with newly diagnosed diabetes, but no significant change in albuminuria and peripheral neuropathy. It may be related to the low awareness of diabetes and insufficient controlled blood glucose, pressure and lipids on target.

Cost of treating diabetic foot ulcers in five different countries.

Most estimates in the literature for the economic cost of treating a diabetic foot ulcer (DFU) are from industrialized countries. There is also marked heterogeneity between the complexity of cases considered in the different studies. The goal of the present article was to estimate treatment costs and costs to patients in five different countries (Chile, China, India, Tanzania, and the United States) for two hypothetical, but well-defined, DFUs at the extreme ends of the complexity spectrum. A co-author, who is a treating physician in the relevant country, was asked to choose treatment plans that represented the typical application of local resources to the DFU. The outcomes were pre-defined as complete healing in case 1 and trans-tibial amputation in case 2, but the time course of treatment was determined by each investigator in a manner that would be typical for their clinic. The costs, in local currencies, for each course of treatment were estimated with the assistance of local hospital administrators. Typical reimbursement scenarios in each country were used to estimate the cost burden to the patient, which was then expressed as a percentage of the annual per capita purchasing power parity-adjusted gross domestic product. There were marked differences in the treatment plans between countries based on the availability of resources and the realities of local conditions. The costs of treatment for case 1 ranged from Int$102 to Int$3959 in Tanzania and in the United States, respectively. The cost for case 2 ranged from Int$3060 to Int$188,645 in Tanzania and in the United States, respectively. The cost burden to the patient varied from the equivalent of 6 days of average income in the United States for case 1 to 5.7 years of average annual income for case 2 in India. Although these findings do not take cost-effectiveness into account, they highlight the dramatic economic burden of a DFU for patients in some countries.

[Clinical characteristics and medical costs of diabetics with amputation at central urban hospitals in China].

OBJECTIVE: To explore the clinical characteristics, medical costs and its influencing factors in diabetics with amputation. METHODS: The data of diabetic amputation for the whole year of 2010 at 39 central municipal Class 3A hospitals all across China were retrospectively analyzed according to a unified protocol, including demographic characteristics, diabetic complications, classification of diabetic foot disease, level and prognosis of amputation and medical costs at hospitals. RESULTS: Among them, 28.2% of all amputated patients or 39.5% of non-traumatic patients were diabetics. There were 313 males and 162 females. The average age and duration of diabetes were (66 ± 12) years and (130 ± 94) months. The level of HbA1c was 8.9% ± 2.4%. Among all amputated diabetics, the concurrent conditions included neuropathy (50.1%), peripheral artery disease (74.8%), nephropathy (28.4%) and retinopathy (25.9%). The patients with foot ulcer at Wagner 4 (50.3%) were more common. Among them, 67.5% had minor amputation with a median hospitalization stay of 33.0 (24.0 - 45.0) days and a medical cost of 26 138 (16 155 - 46 021) yuan RMB. The duration of diabetes, diabetic complications, severity and location of ulcers and amputation level influenced their hospitalization durations and medical costs. CONCLUSION: The patients with diabetes and amputation are elder with more chronic diabetic complications and uncontrolled hyperglycemia. Most of them have complications of local gangrene and require minor amputation at admission. Their hospital stays are longer and medical costs higher significantly correlated with diabetic complications, severity and location of foot ulcers and level of amputations.

[Efficacy of tianmaixiaoke tablets in the treatment of newly diagnosed type 2 diabetes mellitus in China].

OBJECTIVE: To explore the efficacy and influencing factors of chromium picolinate (tianmaixiaoke tablet) in the treatment of newly diagnosed type 2 diabetes mellitus in China. METHODS: A total of 84 outpatients with newly diagnosed type 2 diabetes mellitus visiting 4 hospitals in Beijing were randomly divided into two equal groups: study group receiving tianmaixiaoke tablet 240 mg bid for 24 weeks (n = 42) and control group sitagliptin 100 mg qd for 24 weeks (n = 42). The levels of fasting plasma glucose (FPG), plasma glucose 2 h after meal (PG2 h) and glycated hemoglobin (HbA1c) were detected before and 24 weeks after treatment. The serum levels of chromium and insulin were detected. RESULTS: Study was completed in 76 patients. The serum level of chromium was significantly lower in the diabetes group than in the normal group at baseline ((56 ± 28) µg/L vs (112 ± 21) µg/L, P = 0.00). At 24 weeks after treatment, the levels of HbA1c, FPG and PG2 h decreased while the serum level of chromium increased significantly in both groups. There were 11 patients with changed HbA1c from baseline (ΔHbA1c) ≥ 1% in the study group. At 24 weeks after treatment, HbA1c decreased by 1.61% (from 8.38% ± 0.72% to 6.77% ± 0.62%) and serum level of chromium increased by 35.14 µg/L in the ΔHbA1c ≥ 1% group with a low baseline serum level of chromium ((36.2 ± 18.0) µg/L). Both study group and control group were divided into three subgroups according to baseline serum level of chromium. ΔHbA1c reduced with the increase in baseline serum level of chromium in study group, while in control group, ΔHbA1c was unrelated with baseline serum level of chromium. At 24 weeks after treatment, insulin resistance index (HOMA-IR) reduced, ß cell function index (HOMA-ß) and insulinogenic index (IGI) increased in both groups. Multiple linear regression showed that the variables significantly associated with ΔHbA1c were baseline HbA1c and the baseline serum level of chromium. CONCLUSIONS: Chromium is commonly deficient in the newly diagnosed type 2 diabetics in China. HbA1c decreases and serum chromium increases significantly after chromium supplementation in the patients with a low baseline serum level of chromium.

[Association of a high ankle brachial index with microvascular diseases of diabetes].

OBJECTIVE: To evaluate the association of a high ankle brachial index (ABI) with microvascular diseases of diabetes and to compare its strength with that of a low ABI. METHODS: ABI was obtained in 3293 patients undergoing the screening of chronic complications at the Diabetic Center, No. 306 Hospital of PLA during the period of September 2003 to June 2010. The patient profiles and laboratory data were reviewed. The associations of ABI with microvascular diseases of diabetes were determined by univariate and stepwise Logistic regression analysis. RESULTS: ABI was normal in 3060 patients. 44 had ABI measurements < 0.7, 139 had ABI measurements between 0.7 - 0.9, and 50 had ABI measurements > 1.3. Multivariate analysis indicated that the factors significantly associated with a high ABI were smoking (OR: 2.605; 95%CI: 1.458 - 4.656, P = 0.001) and systolic blood pressure (OR: 1.019; 95%CI: 1.005 - 1.033, P = 0.006). The conditions of nephropathy, neuropathy and retinopathy were not associated with a high ABI. CONCLUSION: Diabetics with a high ABI carry not more adverse atherosclerotic risk factors and suffer no more severe microvascular diabetic complications than those with a normal ABI.

The Prognosis of Diabetic Foot Ulcer is Independent of age? A Comparative Analysis of the Characteristics of Patients with Diabetic Foot Ulcer in Different age Groups: A Cross-Sectional Study from China.

Background: With younger onset age of type 2 diabetes mellitus (T2DM), the incidence of diabetic foot ulcer (DFU) in young and middle-aged adults is also increasing. Elucidating the distinctive characteristics of DFU in different ages and exploring the influence of age on the prognosis of DFU are crucial to the improvement of DFU treatments. Methods: 684 patients hospitalized for DFU in the department of endocrinology were recruited and assigned into the young and middle-aged group (age <65 years old) and the elderly group (age ≥65 years old). Demographic data and clinical features were compared between two groups. Results: Compared with the elderly group, the young and middle-aged group had higher proportion of males (72.3% vs 49.6%, P < .01) and smokers (52.5% vs 35.8%, P < .01), shorter duration of diabetes mellitus (155 months vs 196 months, P < .01), higher levels of glycosylated hemoglobin (9.3% vs 8.7%, P < .01), lower ratio of ankle-brachial index <0.9 (25.8% vs 51.1%, P < .01) and higher levels of c-reactive protein and erythrocyte sedimentation rate (14 mg/L vs 10 mg/L, P < .05; 36 mm/h vs 30 mm/h, P < .05). The prevalence of diabetic peripheral neuropathy and Wagner Grade were similar in two groups. Of note, the prognosis was similar in different age groups, as there were no significant differences in the healing rate (59.7% vs 60.1%, P > .05), healing time (30 days vs 22 days, P > .05) and minor amputation rate (11.9% vs 8.7%, P > .05). Conclusions: We found that no evidence to suggest a better prognosis with younger DFU patients. Compared with elderly ones, young and middle-aged patients were characterized by a higher proportion of smoking, worse glycemic control, higher inflammatory biomarkers but less severe lower limb ischemia, indicating that smoking cessation, strict blood glucose control and early detection of infection were crucial for improving the prognosis of young and middle-aged diabetic DFU patients.

Development and validation of a risk score model for prediction of lower extremity arterial disease in Chinese with type 2 diabetes aged over 50 years.

BACKGROUND: Lower extremity arterial disease (LEAD) is highly prevalent in people with diabetes in China, but half of cases are underdiagnosed due to diversities of clinical presentations and complexities of diagnosis approaches. The purpose of this study was to develop a risk score model for LEAD to facilitate early screening among type 2 diabetes (T2DM) patients. METHODS: A total of 8313 participants with T2DM from the China DIA-LEAD study, a multicenter, cross-sectional epidemiological study, were selected as the training dataset to develop a risk score model for LEAD by logistic regression. The area under receiver operating characteristic curve (AUC) and bootstrapping were utilized for internal validation. A dataset of 287 participants consecutively enrolled from a teaching hospital between July 2017 and November 2017 was used as external validation for the risk score model. RESULTS: A total of 931 (11.2%) participants were diagnosed as LEAD in the training dataset. Factors including age, current smoking, duration of diabetes, blood pressure control, low density lipoprotein cholesterol, estimated glomerular filtration rate, and coexistence of cardio and/or cerebrovascular disease correlated with LEAD in logistic regression analysis and resulted in a weighed risk score model of 0-13. A score of ≥5 was found to be the optimal cut-off for discriminating moderate-high risk participants with AUC of 0.786 (95% CI: 0.778-0.795). The bootstrapping validation showed that the AUC was 0.784. Similar performance of the risk score model was observed in the validation dataset with AUC of 0.731 (95% CI: 0.651-0.811). The prevalence of LEAD was 3.4, 12.1, and 27.6% in the low risk (total score 0-4), moderate risk (total score 5-8), and high risk (total score 9-13) groups of LEAD in the training dataset, respectively, which were 4.3, 19.6, and 30.2% in the validation dataset. CONCLUSION: The weighed risk score model for LEAD could reliably discriminate the presence of LEAD in Chinese with T2DM aged over 50 years, which may be helpful for a precise risk assessment and early diagnosis of LEAD.

Simple-to-use nomogram for evaluating the incident risk of moderate-to-severe LEAD in adults with type 2 diabetes: A cross-sectional study in a Chinese population.

This study aimed to analyze the clinical characteristics of lower extremity atherosclerotic disease (LEAD) in Chinese adult type 2 diabetes (T2D) patients, and also explored the risk factors for LEAD and developed simple-to-use nomograms for LEAD and lesion degree in these patients. We retrospectively studied 4422 patients (male = 2084; female = 2338) with T2D who were ≥50. Based on lower extremity arterial ultrasound findings, we divided the patients into three groups: normal, mild, and moderate-to-severe group. The factors related to LEAD in patients with T2D were analyzed by logistic regression analysis. The risk factors for moderate-to-severe LEAD included: high HbA1c (OR = 1.07 95% CI 1.02-1.13), diabetic peripheral neuropathy (OR = 1.93 95% CI 1.57-2.37), and diabetic retinopathy (OR = 1.26 95%CI 1.01-1.57). The overall areas under the receiver operating characteristic curves for the nomograms for predicting the risks of LEAD and moderate-to-severe LEAD in adult T2D patients were 0.793 (95%CI 0.720, 0.824) and 0.736 (95%CI 0.678, 0.795), respectively. The developed nomograms are simple to use and enable preliminary visual prediction of the risk and degree of LEAD in Chinese T2D patients over 50 years. The nomograms are accurate to a certain degree and provide a clinical basis for predicting the occurrence and progression of LEAD.

Sex-influenced association of metabolic syndrome with lower extremity arterial disease in type 2 diabetes.

AIM: The present study is undertaken to investigate the relationship between metabolic syndrome (MS) and lower extremity arterial disease (LEAD) in type 2 diabetes mellitus (T2DM) patients. METHODS: A multi-center cross-sectional study was conducted on 8374 T2DM patients (4521 males and 3853 females) from 30 hospitals across China from June 2016 to January 2017. The odds ratios (ORs) and 95% confidence intervals (CIs) were presented to show the association between MS and LEAD. The univariate and multiple logistic analyses were performed to examine the association between MS and the prevalence of LEAD. Furthermore, the relationship was analyzed in different sex groups. Subgroup analysis was performed based on the number and individual of MS components. RESULTS: Finally, 1809(21.60%) T2DM patients meet the diagnostic criteria of LEAD. Of the 3853 female subjects, 841(21.83%) patients were in the LEAD group and of the 4521 male subjects, 968(21.41%) patients were in the LEAD group. When adjusting for confounding variables, MS was significantly associated with the prevalence of LEAD in all enrolled T2DM patients (OR = 1.22, 95%CI: 1.09-1.37, P = 0.001). However, upon analyzing LEAD in different sex groups, the significant association remained in females (OR = 1.33, 95%CI: 1.12-1.58, P < 0.001), but not in males (OR = 1.11, 95%CI: 0.95-1.29, P = 0.202). CONCLUSIONS: Our results suggest that MS is specifically associated with an increased risk of LEAD in female T2DM patients. However, MS may not be a significant factor in the prevalence of LEAD in male T2DM patients.

[Postprandial glycemic control using insulin aspart with NPH in inadequately controlled diabetics].

OBJECTIVE: To compare the efficacy and safety of insulin aspart (IAsp) and human insulin (HI) when applied as meal-time insulin with neutral protamine Hagedorn insulin (NPH) at bedtime in diabetics. METHODS: A total of 220 Chinese subjects with type 1 or type 2 diabetes from 5 different hospitals were randomized by a ratio of 1:1 into two groups accepting IAsp or HI combined with NPH respectively. The main endpoints were assessed by fasting plasma glucose (FPG), 2 hour postprandial plasma glucose (2 h PPG), HbAlc and hypoglycemia. RESULTS: A greater reduction in mean 2 h PPG was achieved in the IAsp group [(14.6 +/- 5.3) mmol/L] as compared with the HI group [(8.4 +/- 4.1) mmol/L] (P < 0.01, adjusted for baseline value, center effect and diabetes type). Significantly more IAsp-treated subjects reached the 2 h PPG target (50.0% vs 25.5%, P < 0.01). HbA1c was reduced more in IAsp/NPH group [(9.3 +/- 1.4)% vs (7.7 +/- 1.3)%] than in HI/NPH group [(9.2 +/- 1.2)% vs (7.7 +/- 1.2)%]. HbA1c target was reached by 24.5% (IAsp) vs 14.5% (HI) of subjects (P < 0.05). No major hypoglycemia or serious adverse events were observed for the IAsp group. Lower incidence of nocturnal hypoglycemia (IAsp/NPH: 3% vs HI/NPH: 4%) was reported in the IAsp group. Average daily insulin doses were 0.60/0.23 (IAsp/NPH) and 0.65/0.24 (HI/NPH) IU/kg respectively. CONCLUSION: Treatment of IAsp in basal-bolus therapy in combination with NPH provides a superior postprandial glucose control and allows more subjects to reach the glycemic target without elevating the nocturnal hypoglycemic risk or adverse events.

[Features of insulin secretion and insulin resistance in newly diagnosed type 2 diabetes of different body mass indices].

OBJECTIVE: To investigate insulin secretion function and insulin resistance in Chinese newly diagnosed type 2 diabetes (obese and non-obese patients) in order to provide evidence for clinical treatment. METHODS: 408 newly diagnosed type 2 diabetes and 40 normal controls were recruited. Height, weight were measured, insulin and glucose of 0 min, 30 min, 60 min, 120 min during oral glucose tolerance test were examined. The patients with fasting glucose level greater than 8.3mmol/L were treatment with Gliclazide for 1 - 3 months. After normalization of the plasma glucose levels for more than 2 weeks, and withdraw this medication for 48 hours, then OGTT were repeated to assess IR and IS. RESULTS: The patients were divided into four groups based on fasting plasma glucose (DM1: FPG < 6.9mmol/L; DM2: 6.9 mmol/L < or = FPG < 8.3 mmol/L; DM3: 8.3 mmol/L < or = FPG < 9.7 mmol/L; DM4: FPG > or = 9.7 mmol/L). Every groups were further stratified to subgroups by cut point of BMI = 24 kg/m(2). Their insulin sensitivity and insulin secretion function compared between subgroups. (1) True insulin level in BMI > or = 24 (FPG < 6.9 mmol/L) subgroups were higher than control's (3.5 +/- 0.5 vs 3.2 +/- 0.6 natural logarithm) (P < 0.05). (2) In BMI > or = 24 subgroups, their insulin sensitivity were even worse than BMI < 24 groups', but their insulin secretion function were better at the same FPG level. (3) After intervention, the change of insulin sensitivity in BMI < 24 group was better than BMI > or = 24 group's (-4.7 +/- 0.9 vs -5.5 +/- 1.4 natural logarithm) (P < 0.05); but the change of insulin secretion function in BMI < 24 group was worse. CONCLUSION: (1) In newly diagnostic type 2 diabetes, insulin sensitivity and insulin secretion function were decreased with the increase of FPG, but they were different between obese and non-obese group. (2) Insulin secretion function was recovered better in obese group when eliminated glucose toxicity.

Direct medical costs for patients with type 2 diabetes in 16 tertiary hospitals in urban China: A multicenter prospective cohort study.

AIMS/INTRODUCTION: To investigate the direct medical costs for patients with type 2 diabetes in China and to examine the influencing factors. MATERIALS AND METHODS: In the present multicenter study, 1,070 patients with type 2 diabetes from 16 tertiary hospitals in 14 major cities of China were enrolled. Patient data and direct medical costs were collected during a follow-up period of 6 months at intervals of 1 month. The log-transformed direct medical costs were fitted by a generalized estimation equation to indicator variables for demographics, metabolic control, treatments, complications and comorbidities. RESULTS: Data of 871 participants were included in the analysis. The mean annual total direct medical costs and outpatient medical costs were $1,990.20 and $1,687.20 respectively. The average costs per inpatient per admission were $2,127.10. The share of out-of-pocket for total medical costs, outpatient costs and cost per inpatient per admission were 45.4, 46.3 and 26.0% respectively. Independent determinants of total medical costs were diabetes duration, dyslipidemia and diabetic complications, such as neuropathy and nephropathy, as well as diabetes treatment, such as the use of glucagon-like peptide-1 receptor agonists. Costs showed prominent variation across centers. CONCLUSIONS: Diabetes is imposing a growing economic burden in patients with type 2 diabetes in China. Diabetes-related complications and comorbidities have a great impact on the medical costs. As different health policies, economic development and regional health inequalities also have an important influence on the direct medical cost, healthcare reform needs to optimize resource allocation in health service delivery systems, and provide more equitable and affordable healthcare.