Predicting the risk of future diabetic foot ulcer occurrence: a prospective cohort study of patients with diabetes in Tanzania

Objectives The aim of this study was to identify the parameters that predict the risk of future foot ulcer occurrence in patients with diabetes.Research design and methods 1810 (male (M)/female (F): 1012/798) patients, with no foot ulcer at baseline, participated in this study. Data from a set of 28 parameters were collected at baseline. During follow- up, 123 (M/F: 68/55) patients ulcerated. Survival analyses together with logistic regression were used to identify the parameters that could predict the risk of future diabetic foot ulcer occurrence.Results A number of parameters (HR (95% CI)) including neuropathy (2.525 (1.680 to 3.795)); history of ulceration (2.796 (1.029 to 7.598)); smoking history (1.686 (1.097 to 2.592)); presence of callus (1.474 (0.999 to 2.174)); nail ingrowth (5.653 (2.078 to 15.379)); foot swelling (3.345 (1.799 to 6.218)); dry skin (1.926 (1.273 to 2.914)); limited ankle (1.662 (1.365 to 2.022)) and metatarsophalangeal (MTP) joint (2.745 (1.853 to 4.067)) ranges of motion; and decreased (3.141 (2.102 to 4.693)), highly decreased (5.263 (1.266 to 21.878)), and absent (9.671 (5.179 to 18.059)) sensation to touch; age (1.026 (1.010 to 1.042)); vibration perception threshold (1.079 (1.060 to 1.099)); duration of diabetes (1.000 (1.000 to 1.000)); and plantar pressure at the first metatarsal head (1.003 (1.001 to 1.005)), temperature sensation (1.019 (1.004 to 1.035)) and temperature tolerance (1.523 (1.337 to 1.734)) thresholds to hot stimuli and blood sugar level (1.027 (1.006 to 1.048)) were all significantly associated with increased risk of ulceration. However, plantar pressure underneath the fifth toe (0.990 (0.983 to 0.998)) and temperature sensation (0.755 (0.688 to 0.829)) and temperature tolerance (0.668 (0.592 to 0.0754)) thresholds to cold stimuli showed to significantly decrease the risk of future ulcer occurrence. Multivariate survival model indicated that nail ingrowth (4.42 (1.38 to 14.07)); vibration perception threshold (1.07 (1.04 to 1.09)); dry skin status (4.48 (1.80 to 11.14)); and temperature tolerance threshold to warm stimuli (1.001 (1.000 to 1.002)) were significant predictors of foot ulceration risk in the final model. The mean time to ulceration was significantly (p<0.05) shorter for patients with: dry skin (χ2=11.015), nail ingrowth (χ2=14.688), neuropathy (χ2=21.284), or foot swelling (χ2=16.428).Conclusion Nail ingrowth and dry skin were found to be strong indicators of vulnerability of patients to diabetic foot ulceration. Results highlight that assessments of neuropathy in relation to both small and larger fiber impairment need to be considered for predicting the risk of diabetic foot ulceration

Predicting the risk of amputation and death in patients with diabetic foot ulcer. A long‐term prospective cohort study of patients in Tanzania

IntroductionThis prospective cohort study aimed to identify the characteristics of patients with diabetic foot ulcer who are at higher risk of amputation and at increased risk of death.MethodsAbout 103(M/F:60/43) participants, with active foot ulcer at baseline, participated in this study and followed for 22 years till death or lost to follow-up. Ten clinical measures were collected at baseline. During the follow-up of 4.2 ± 5.4 years, 22(M/F:14/8) participants had an amputation and 50(M/F:32/18) participants passed away during 5.5 ± 5.8 years follow-up period.ResultsCox Proportional Hazard regression (HR[95%CI]) indicated neuropathy (6.415[1.119–36.778]); peripheral arterial disease (PAD) (9.741[1.932– 49.109]); current smoking (16.148[1.658–157.308]); diabetes type- 1 (3.228[1.151–9.048]) and longer delay attending appointment after ulcer (1.013[1.003–1.023]) were significantly (p < .05) associated with increased risk of amputation. In addition, death was significantly associated with the risk of amputation (3.458[1.243–9.621]). Three parameters (HR[95%CI]) including neuropathy (3.058[1.297–7.210]); PAD (5.069[2.113–12.160]); amputation history (3.689[1.306–10.423]) and retinopathy (2.389[1.227–4.653]) were all significantly associated with increased risk of death. Kaplan–Meier survival analyses indicates that the time to amputation in years for participants who eventually died was significantly shorter (11.122 ± 1.507) vs those who stayed alive (15.427 ± 1.370).ConclusionNeuropathy and PAD were the only two characteristics that increased both the risk of amputation and death. Amputation showed to contribute to an increased risk of death and those participants who eventually died had a higher risk of amputation. Delay in attending appointments after ulceration is shown to increase the risk of amputation. In addition, the participants with PAD showed a significantly shorter time to both amputation and death while neuropathy was only associated with decreased time to death. Amputation history and death during follow-up decrease the time to death and amputation respectively

What characteristics are most important in stratifying patients into groups with different risk of diabetic foot ulceration?

Aims/Introduction: This study aimed to assess if patients can be divided into different strata, and to explore if these correspond to the risk of diabetic foot complications. Materials and Methods: A set of 28 demographic, vascular, neurological and biomechanical measures from 2,284 (1,310 men, 974 women) patients were included in this study. A two‐step cluster analysis technique was utilised to divide the patients into groups, each with similar characteristics. Results: Only two distinct groups: group 1 (n = 1,199; 669 men, 530 women) and group 2 (n = 1,072; 636 men, 436 women) were identified. From continuous variables, the most important predictors of grouping were: ankle vibration perception threshold (16.9 ± 4.1 V vs 31.9 ± 7.4 V); hallux vibration perception threshold (16.1 ± 4.7 V vs 33.1 ± 7.9 V); knee vibration perception threshold (18.2 ± 5.1 V vs 30.1 ± 6.5 V); average temperature sensation threshold to cold (29.2 ± 1.1°C vs 26.7 ± 0.7°C) and hot (35.4 ± 1.8°C vs 39.5 ± 1.0°C) stimuli, and average temperature tolerance threshold to hot stimuli at the foot (43.4 ± 0.9°C vs 46.6 ± 1.3°C). From categorical variables, only impaired sensation to touch was found to have importance at the highest levels: 87.4% of those with normal sensation were in group 1; whereas group 2 comprised 95.1%, 99.3% and 90.5% of those with decreased, highly‐decreased and absent sensation to touch, respectively. In addition, neuropathy (monofilament) was a moderately important predictor (importance level 0.52) of grouping with 26.2% of participants with neuropathy in group 1 versus 73.5% of participants with neuropathy in group 2. Ulceration during follow up was almost fivefold higher in group 2 versus group 1. Conclusions: Impaired sensations to temperature, vibration and touch were shown to be the strongest factors in stratifying patients into two groups with one group having almost 5‐fold risk of future foot ulceration compared to the other

Predicting the risk of amputation and death in patients with diabetic foot ulcer. A long‐term prospective cohort study of patients in Tanzania

Introduction This prospective cohort study aimed to identify the characteristics of patients with diabetic foot ulcer who are at higher risk of amputation and at increased risk of death. Methods About 103(M/F:60/43) participants, with active foot ulcer at baseline, participated in this study and followed for 22 years till death or lost to follow-up. Ten clinical measures were collected at baseline. During the follow-up of 4.2 ± 5.4 years, 22(M/F:14/8) participants had an amputation and 50(M/F:32/18) participants passed away during 5.5 ± 5.8 years follow-up period. Results Cox Proportional Hazard regression (HR[95%CI]) indicated neuropathy (6.415[1.119–36.778]); peripheral arterial disease (PAD) (9.741[1.932– 49.109]); current smoking (16.148[1.658–157.308]); diabetes type- 1 (3.228[1.151–9.048]) and longer delay attending appointment after ulcer (1.013[1.003–1.023]) were significantly (p < .05) associated with increased risk of amputation. In addition, death was significantly associated with the risk of amputation (3.458[1.243–9.621]). Three parameters (HR[95%CI]) including neuropathy (3.058[1.297–7.210]); PAD (5.069[2.113–12.160]); amputation history (3.689[1.306–10.423]) and retinopathy (2.389[1.227–4.653]) were all significantly associated with increased risk of death. Kaplan–Meier survival analyses indicates that the time to amputation in years for participants who eventually died was significantly shorter (11.122 ± 1.507) vs those who stayed alive (15.427 ± 1.370). Conclusion Neuropathy and PAD were the only two characteristics that increased both the risk of amputation and death. Amputation showed to contribute to an increased risk of death and those participants who eventually died had a higher risk of amputation. Delay in attending appointments after ulceration is shown to increase the risk of amputation. In addition, the participants with PAD showed a significantly shorter time to both amputation and death while neuropathy was only associated with decreased time to death. Amputation history and death during follow-up decrease the time to death and amputation respectively

The Charcot Foot: An Emerging Public Health Problem for African Diabetes Patients

Background: Although the awareness, diagnosis, management of the complications associated with diabetes have improved in African countries over the past decade, surveillance activities in Tanzania and anecdotal reports from other African countries have suggested an increased prevalence of Charcot Neuroarthropathy (CN) over the past few years. Aim: To characterize the epidemiology and the clinical burden of CN in a large diabetes population in Tanzania, and to evaluate outcomes of persons with the condition. Methods: This was a prospective analytic cohort study conducted between January 2013 through December 2015. Following informed consent, patients were followed at the outpatient clinic. Detailed clinical assessments and documented presence of diabetic peripheral neuropathy (DPN), macrovascular disease and microvascular disease were recorded. Education and counselling were part of the follow-up program. Results: 3,271 ulcerations were presented at the clinic during the 3-year study period. 571 (18%) met the case definition for CN; all patients had Type 2 diabetes. The prevalence for each of the years 2013, 2014, and 2015 was 19/1192 (1.6%), 209/1044 (20%), and 343/1035 (34%), respectively; the increases in the slope of the trendline was statistically significant (p<0.001). Conclusion: The prevalence of CN is increasing in the Tanzanian diabetes patient population, and is strongly associated with neuropathy. CN can lead to severe deformity, disability, and amputation. Due to the risk of limb amputation, patients with diabetes must seek immediate care if signs or symptoms appear and avoid delay in seeking medical attention. Early diagnosis of CN by caregivers is extremely important for successful outcomes

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

Microalbuminuria among Type 1 and Type 2 diabetic patients of African origin in Dar Es Salaam, Tanzania

BACKGROUND: The prevalences and risk factors of microalbuminuria are not full described among black African diabetic patients. This study aimed at determining the prevalence of microalbuminuria among African diabetes patients in Dar es Salaam, Tanzania, and relate to socio-demographic features as well as clinical parameters. METHODS: Cross sectional study on 91 Type 1 and 153 Type 2 diabetic patients. Two overnight urine samples per patient were analysed. Albumin concentration was measured by an automated immunoturbidity assay. Average albumin excretion rate (AER) was used and were categorised as normalbuminuria (AER < 20 ug/min), microalbuminuria (AER 20–200 ug/min), and macroalbuminuria (AER > 200 ug/min). Information obtained also included age, diabetes duration, sex, body mass index, blood pressure, serum total cholesterol, high-density and low-density lipoprotein cholesterol, triglycerides, serum creatinine, and glycated hemoglobin A(1c). RESULTS: Overall prevalence of microalbuminuria was 10.7% and macroalbuminuria 4.9%. In Type 1 patients microalbuminuria was 12% and macroalbuminuria 1%. Among Type 2 patients, 9.8% had microalbuminuria, and 7.2% had macroalbuminuria. Type 2 patients with abnormal albumin excretion rate had significantly longer diabetes duration 7.5 (0.2–24 yrs) than those with normal albumin excretion rate 3 (0–25 yrs), p < 0.001. Systolic and diastolic blood pressure among Type 2 patients with abnormal albumin excretion rate were significantly higher than in those with normal albumin excretion rate, (p < 0.001). No significant differences in body mass index, glycaemic control, and cholesterol levels was found among patients with normal compared with those with elevated albumin excretion rate either in Type 1 or Type 2 patients. A stepwise multiple linear regression analysis among Type 2 patients, revealed AER (natural log AER) as the dependent variable to be predicted by [odds ratio (95% confidence interval)] diabetes duration 0.090 (0.049, 0.131), p < 0.0001, systolic blood pressure 0.012 (0.003–0.021), p < 0.010 and serum creatinine 0.021 (0.012, 0.030). CONCLUSION: The prevalence of micro and macroalbuminuria is higher among African Type 1 patients with relatively short diabetes duration compared with prevalences among Caucasians. In Type 2 patients, the prevalence is in accordance with findings in Caucasians. The present study detects, however, a much lower prevalence than previously demonstrated in studies from sub-Saharan Africa. Abnormal AER was significantly related to diabetes duration and systolic blood pressure

Can a combination of lifestyle and clinical characteristics explain the presence of foot ulcer in patients with diabetes?

AimsThe aim of this study was to identify the biomechanical, neurological and clinical parameters along with other demographics and lifestyle risk factors that could explain the presence of foot ulcer in patients with diabetes in Africa.MethodsA total of 1270 (M/F:696/574) patients; 77(M/F:53/24) with ulcerated vs 1193 (M/F: 643/550) with non-ulcerated feet; participated in this study. A set of 28 parameters were collected and compared between the participants with and without active foot ulcers. Multivariate logistic regression was utilised to develop an explanatory model for foot ulceration.ResultsFoot swelling (χ2(1,n = 1270) = 265.9,P = 0.000,Phi = 0.464) and impaired sensation to monofilament (χ2(2,n = 1270) = 114.2,P = 0.000,Cramer'sV = 0.300) showed strong association with presence of ulceration. A lower Temperature sensitivity to cold stimuli and limited ankle joint mobility were observed to be significant (P < 0.05) contributors to ulceration. The logistic regression model can justify the presence of foot ulceration with 95.3% diagnostic accuracy, 99.1% specificity and 37.3% sensitivity.ConclusionParticipants with ulcerated foot show distinct characteristics in few foot related parameters. Swollen foot, limited ankle mobility, and peripheral sensory neuropathy were significant characteristics of patients with diabetic foot ulcer. One out of three patients with ulcerated foot showed common characteristics that could be justified by the model

Tropical diabetic hand syndrome: Risk factors in an adult diabetes population

AbstractObjectives: To determine risk factors for the tropical diabetic hand syndrome, a condition associated with significant morbidity and mortality in Africa.Methods: This was a case-control study of a Tanzanian diabetes population presenting with the syndrome during February 1998 to March 2000. A case patient was defined as any patient with diabetes presenting with hand cellulitis, ulceration, or gangrene. Control patients were randomly selected patients with diabetes who had no hand symptoms.Results: Thirty-one case patients and 96 control patients were identified. The median age of case patients was 52 years (range, 28–76 y); 58% were male; 4 patients (16%) died. Precipitating events included papule (n = 6), insect bites (n = 6), boils (n = 5), burns (n = 2), or trauma (n = 3). Case and control patients were similar for presence of micro- and macrovascular disease and occupation. On logistic regression analysis, independent risk factors were body mass index of 20 or less (odds ratio [OR] = 18.0; 95% confidence interval [CI] = 4.3−97.0; P < 0.001), peripheral neuropathy (OR = 23.0; 95% Cl = 5.3−124.0; P < 0.001), or type I diabetes, (OR = 6.7; 95% Cl = 2.0−24.0, P < 0.01).Conclusion: The major risk factors for the tropical diabetic hand syndrome are intrinsically related to the underlying disease. Thus, prevention of hand infections may require aggressive glucose control, and education on hand care and the importance of seeing a doctor promptly at the onset of symptoms