Hypoglycemia is common in individuals with type 1 diabetes, especially during exercise. We investigated the accuracy of two different continuous glucose monitoring systems during exercise-related ...hypoglycemia in an experimental setting.
Fifteen individuals with type 1 diabetes participated in two separate euglycemic-hypoglycemic clamp days (Clamp-exercise and Clamp-rest) including five phases: 1) baseline euglycemia, 2) plasma glucose (PG) decline ± exercise, 3) 15-minute hypoglycemia ± exercise, 4) 45-minute hypoglycemia, and 5) recovery euglycemia. Interstitial PG levels were measured every five minutes, using Dexcom G6 (DG6) and FreeStyle Libre 1 (FSL1). Yellow Springs Instruments 2900 was used as PG reference method, enabling mean absolute relative difference (MARD) assessment for each phase and Clarke error grid analysis for each day.
Exercise had a negative effect on FSL1 accuracy in phase 2 and 3 compared to rest (ΔMARD = +5.3 percentage points (95% CI): 1.6, 9.1 and +13.5 percentage points 6.4, 20.5, respectively). In contrast, exercise had a positive effect on DG6 accuracy during phase 2 and 4 compared to rest (ΔMARD = -6.2 percentage points -11.2, -1.2 and -8.4 percentage points -12.4, -4.3, respectively). Clarke error grid analysis showed a decrease in clinically acceptable treatment decisions during Clamp-exercise for FSL1 while a contrary increase was observed for DG6.
Physical exercise had clinically relevant impact on the accuracy of the investigated continuous glucose monitoring systems and their ability to accurately detect hypoglycemia.
Aim The aim of this study was to investigate safety of treating diabetic foot ulcers with a topically administered mesenchymal stem cell product. Method Individuals with diabetes, peripheral ...neuropathy, toe blood pressure > 39 mmHg and non-infected foot ulcers with duration of four to fifty-two weeks were screened. Participants were treated with a one-time application of a topically applied allogeneic cellular product containing CD362 enriched mesenchymal stem cells suspended in a collagen solution. Participants were subsequently followed for seven months to gather information on adverse event and serious adverse events. Results/discussion A total of sixteen individuals were screened, of whom two were included. The included participants incurred a total of seven adverse events and one serious adverse event. Increased exudation from the treated diabetic foot ulcer was observed for both participants and a connection to investigational medicinal product was suspected. The increased exudation was resolved within one week after application of investigational medicinal product, without any further complications. The serious adverse event consisted of a hospital admission due to neurological symptoms, which were assumed to be caused by hypoglycemia, with no suspected correlation to the investigational medicinal product. None of the other observed adverse events were suspected to be associated with the investigational medicinal product. Conclusion This study presents data from two individuals with a diabetic foot ulcer treated with a novel topical mesenchymal stem cell product. An adverse event observed for both participants was suspected to be associated to the investigational medicinal product, i.e., increased exudation, which was resolved within one week, did not lead to further complications and can easily be remedied by choosing bandages with higher absorption capacity or increasing frequency of bandage changes. This study lays the groundwork for further large scale randomized clinical studies. Trial registration: EudraCT number 2015-005580-16. Registered 12/06-2018. Keywords: Diabetic foot, Mesenchymal stem cells, Clinical trial phase I, Safety
Diabetes mellitus is associated with serious complications, with foot ulcers and amputation of limbs among the most debilitating consequences of late diagnosis and treatment of foot ulcers. Thus, ...prediction and on-time treatment of diabetic foot ulcers (DFU) are of great importance for improving and maintaining patients' quality of life and avoiding the consequent socio-economical burden of amputation. In this study, we use Danish national registry data to understand the risk factors of developing diabetic foot ulcers and amputation among patients with diabetes. We analyze the data of 246,705 patients with diabetes to assess some of the main risk factors for developing DFU/amputation. We study the socioeconomic information and past medical history of the patients. Factors, such as low family disposable income, cardiovascular disorders, peripheral artery, neuropathy, and chronic renal complications are among the important risk factors. Mental disorders and depression, albeit not as pronounced, still pose higher risks in comparison to the group of people without these complications. We further use machine learning techniques to assess the practical usefulness of such risk factors for predicting foot ulcers and amputation. Finally, we outline the limitations of working with registry data sources and explain potentials for combining additional public and private data sources in future applications of artificial intelligence (AI) to improve the prediction of diabetic foot ulcers and amputation.
The aim of this study was to evaluate outcomes of needle tenotomies as a treatment option for hammer, mallet and claw toes in patients with diabetes.
This was a retrospective study where all patients ...receiving flexor tendon tenotomy by needle at our outpatient clinic were identified through the electronic patient record system.
A total of 81 patients that had 106 tenotomy procedures performed were identified. The 81 included (68% male) had an average age of 65.4 years, and 27 (33%) had Type 1 diabetes. Of the 106 procedures 36 were performed due to an ulcer on the feet. Of the 36 treated ulcers, 34 (94%) healed in an average time of 28 days. Tenotomies performed to prevent impending ulcers from progressing to active ulcers, were performed 84 times in total. Of the 84 procedures 6 patients progressed to an active ulcer. No serious complications i.e. infections or amputations in relation to the procedure were registered.
Needle flexor tenotomies are a relatively safe and effective treatment compared to tenotomies done by scalpel, both as treatment for ulcers and to prevent formation of new ulcers associated with hammer, mallet and claw toe deformities. As a side note, transfer lesions are avoidable if all toes on one or both feet are tenotomized in one procedure.
OBJECTIVE: The purpose of this study was to estimate the progression rates to impaired glucose regulation (impaired fasting glucose or impaired glucose tolerance) and diabetes in the Danish ...population-based Inter99 study and in a high-risk subpopulation, separately. RESEARCH DESIGN AND METHODS: From a population-based primary prevention study, the Inter99 study, 4,615 individuals without diabetes at baseline and with relevant follow-up data were divided into a low- and a high-risk group based on a risk estimate of ischemic heart disease or the presence of risk factors (smoking, hypertension, hypercholesterolemia, obesity, or impaired glucose tolerance). High-risk individuals (57.1%) were examined with an oral glucose tolerance test at 1 and 3 years, and all of the participants were reexamined at the 5-year follow-up. Person-years at risk were calculated. Progression rates to impaired glucose regulation and diabetes were estimated directly from baseline to the 5-year follow-up for all the participants and from baseline through the 1- and 3- to 5-year follow-up examinations for the high-risk individuals, separately. RESULTS: In the combined low- and high-risk group, 2.1 individuals per 100 person-years progressed from normal glucose tolerance (NGT) to impaired glucose regulation or diabetes. Among high-risk individuals, 5.8 per 100 person-years with NGT progressed to impaired glucose regulation or diabetes, and 4.9 per 100 person-years progressed from impaired glucose regulation to diabetes. CONCLUSIONS: Progression rates to impaired glucose regulation using the current World Health Organization classification criteria were calculated for the first time in a large European population-based study. The progression rates to diabetes show the same pattern as seen in the few similar European studies.
The Charcot Foot and Mortality from 2000 to 2016 ENGBERG, SUSANNE; KIRKETERP-MØLLER, KLAUS; RASMUSSEN, ANNE
Diabetes (New York, N.Y.),
07/2018, Letnik:
67, Številka:
Supplement_1
Journal Article
Recenzirano
Introduction: The Charcot foot is a relatively rare but serious foot complication in patients with diabetes and neuropathy. The aim was to study the mortality and compare baseline characteristics at ...diagnosis between Charcot patients who died or survived during follow-up.
Materials and Methods: A retrospective cohort study including all patients with a Charcot diagnosis at our centre from 2000 to 2016. Poisson regression analyses were done.
Results: A total of 164 patients had the diagnosis Charcot (DM146) and 52 (31.1%) died during follow-up. They lived for 1973 days (range: 219-4895) i.e., 5.4 years. Patients were followed for 1122 years in total, median 6.0 years/patient (Q1-Q3=3.2-10.0). The mortality rate was 4.6/100 person-years-at-risk. Patients who died were significantly older (61±10 vs. 54±11 years), had less often type 1 diabetes (40 (27-55) vs. 60% (50-70)), were less often non-smokers (35 (22-49) vs. 52% (42-61)), had a lower hemoglobin (7.9±1.2 vs. 8.3±0.9), a higher creatinine (114 88-161 vs. 85 69-109) and were more often treated with antitrombotic agents (71 (57-83) vs. 53% (43-62)) compared to survivors. Rate ratios for death were insignificantly different among smokers and non-smokers, among patients with type 1 and 2 diabetes, among patients with a diabetes duration below or above 10 years and among patients with HbA1c above or below 60 mmol/mol-both in univariate analyses and after adjustment for age and gender.
Conclusion: The mortality rate among patients with Charcot feet was 4.6%/person-years-at-risk and was not affected by diabetes type, smoking, diabetes duration or HbA1c-level.
Disclosure
S. Engberg: None. K. Kirketerp-Møller: None. A. Rasmussen: None.
We designed a systematic literature review to identify available evidence on adherence to and persistence with antidiabetic medication in people with type 2 diabetes (T2D). Electronic screening and ...congress searches identified real‐world noninterventional studies (published between 2010 and October 2020) reporting estimates of adherence to and persistence with antidiabetic medication in adults with T2D, and associations with glycaemic control, microvascular and/or macrovascular complications, hospitalizations and healthcare costs. Ninety‐two relevant studies were identified, the majority of which were retrospective and reported US data. The proportions of patients considered adherent (median range 51.2% 9.4%‐84.3%) or persistent (median range 47.7% 16.9%‐94.0%) varied widely across studies. Multiple studies reported an association between greater adherence/persistence and greater reductions in glycated haemoglobin levels. Better adherence/persistence was associated with fewer microvascular and/or macrovascular outcomes, although there was little consistency across studies in terms of which outcomes were improved. More adherent and more persistent patients were typically less likely to be hospitalized or to have emergency department visits/admissions and spent fewer days in hospital annually than less adherent/persistent patients. Greater adherence and persistence were generally associated with lower hospitalization costs, higher pharmacy costs and lower or budget‐neutral total healthcare costs compared with lower adherence/persistence. In conclusion, better adherence and persistence in people with T2D is associated with lower rates of microvascular and/or macrovascular outcomes and inpatient hospitalization, and lower or budget‐neutral total healthcare expenditure. Education and treatment strategies to address suboptimal adherence and persistence are needed to improve clinical and economic outcomes.
Summary Background ONWARDS 6 compared the efficacy and safety of once-weekly subcutaneous insulin icodec (icodec) and once-daily insulin degludec (degludec) in adults with type 1 diabetes. Methods ...This 52-week (26-week main phase plus a 26-week safety extension), randomised, open-label, treat-to-target, phase 3a trial was done at 99 sites across 12 countries. Adults with type 1 diabetes (glycated haemoglobin HbA1c <10·0% 86 mmol/mol) were randomly assigned (1:1) to once-weekly icodec or once-daily degludec, both in combination with insulin aspart (two or more daily injections). The primary endpoint was change in HbA1c from baseline to week 26, tested for non-inferiority (0·3 percentage point margin) in all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04848480, and is now complete. Findings Between April 30 and Oct 15, 2021, of 655 participants screened, 582 participants were randomly assigned to icodec (n=290) or degludec (n=292). At week 26, from baseline values of 7·59% (icodec) and 7·63% (degludec), estimated mean changes in HbA1c were −0·47 percentage points and −0·51 percentage points, respectively (estimated treatment difference 0·05 percentage points 95% CI −0·13 to 0·23), confirming non-inferiority of icodec to degludec (p=0·0065). Overall rate of combined clinically significant or severe hypoglycaemia (baseline to week 26) was statistically significantly higher with icodec than degludec (19·9 vs 10·4 events per patient-year of exposure; estimated rate ratio 1·9 95% CI 1·5 to 2·3; p<0·0001). The rate was also statistically significantly higher with icodec than degludec when evaluated over 57 weeks (52 weeks plus a 5-week follow-up period). 39 serious adverse events were reported in 24 (8%) participants receiving icodec, and 25 serious adverse events were reported in 20 (7%) participants receiving degludec. One participant in the icodec group died; this was judged unlikely to be due to the trial product. Interpretation In adults with type 1 diabetes, once-weekly icodec showed non-inferiority to once-daily degludec in HbA1c reduction at week 26, with statistically significantly higher rates of combined clinically significant or severe hypoglycaemia. For icodec, time below 3·0 mmol/L (<54 mg/dL) was at the threshold of the internationally recommended target (<1%) during weeks 22–26 and below target during weeks 48–52. Funding Novo Nordisk.
The impact of hypoglycemia, hyperglycemia and glycemic variability on cardiac arrhythmia susceptibility in people with type 1 diabetes is uncertain. We performed a 12-month prospective observational ...study employing continuous glucose monitoring and implantable loop recorders to investigate potential associations between glycemia and cardiac arrhythmias. Thirty adults with type 1 diabetes (mean ± SD age 63 ± 8 years, BMI 26 ± 5 kg/m2, HbA1c 7.3 ± 1.1% 56.9 ± 11.9 mmol/mol) and without any history of cardiac arrhythmias were included. Daytime and nighttime incidence rate ratios (IRR) of arrhythmias were determined for hypoglycemia (interstitial glucose (IG) < 3.9 mmol/L), hyperglycemia (IG > 10.0 mmol/L), and glycemic variability (standard deviation and coefficient of variation). Hypoglycemia was not associated with an increased risk of cardiac arrhythmias in comparison with euglycemia (IG 3.9 - 10.0 mmol/L) and hyperglycemia. However, during daytime, a trend of increased risk of arrhythmias was observed when comparing hypoglycemia with euglycemia (IRR 1.08 95% CI 0.99 - 1.18). Furthermore, during daytime both the occurrence of hyperglycemia and time spent in hyperglycemia within the same hour of an arrhythmia were associated with an increased risk of arrhythmias compared to euglycemia (IRR 2.03 95% CI 1.21 - 3.40 and IRR 1.07 95% CI 1.02 - 1.13, respectively). Nighttime hypoglycemia and hyperglycemia were not associated with increased risk of arrhythmias. Increased glycemic variability was not associated with an increased risk of arrhythmias during daytime, whereas a reduced risk was observed during nighttime. In conclusion, daytime hypoglycemia and hyperglycemia may contribute to an increased risk of cardiac arrhythmias compared to euglycemia, in people with type 1 diabetes. No associations were found between glycemic levels and cardiac arrhythmias during nighttime, indicating diurnal differences in arrhythmogenic susceptibility.
Disclosure
P.G.Hagelqvist: None. T.Vilsbøll: Consultant; AstraZeneca, Boehringer Ingelheim Inc., Gilead Sciences, Inc., Eli Lilly and Company, Mundipharma, Merck & Co., Inc., Novo Nordisk A/S, Sanofi, Sun Pharmaceutical Industries Ltd., Bristol-Myers Squibb Company. A.Andersen: None. K.Maytham: None. C.R.Andreasen: None. S.Engberg: Employee; Novo Nordisk A/S. T.B.Lindhardt: None. J.Forman: None. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi, Vertex Pharmaceuticals Incorporated. F.K.Knop: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Lundbeck.
Funding
Novo Nordisk Foundation (28300)
The aim of this study was to evaluate the effects of needle flexor tendon tenotomy treatment of the diabetic hammertoe deformity.
A multicenter randomized controlled trial of individuals with ...diabetes and ulcers or impending ulcers associated with hammertoes was performed between 1 November 2019 and 31 March 2021. Participants were stratified by the presence of ulcers or impending ulcers. Participants were randomly assigned to tenotomy and standard nonsurgical treatment or to standard nonsurgical treatment alone. Primary outcomes were time to ulcer healing and progression from impending ulcer to active ulcer.
Of 224 screened participants with diabetes, 95 (59.0% men) were included. The mean follow-up was 291 ± 70 days, 28 (29.5%) had type 1 diabetes, mean diabetes (presented with 25-75% quartile) duration was 20 (13-26) years, and mean age was 67.7 ± 9.8 years. Of the included participants, 16 had ulcers, of whom 8 were randomly assigned to intervention. Of the remaining 79 with impending ulcers, 39 were randomly assigned to intervention. For participants with ulcers, healing rates favored tenotomy (100% vs. 37.5%, P = 0.026) as did time to ulcer healing (P = 0.04). For those with impending ulcers, incidence of progression to an active ulcer was lower (1 vs. 7, P = 0.028) and the number of ulcer-free days higher (P = 0.043) in the tenotomy group. No serious adverse events were recorded.
This randomized study showed that the simple procedure of needle flexor tendon tenotomy was effective and safe when treating and preventing ulcers associated with the diabetic hammertoe deformity.
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