Human Achilles tendon glycation and function in diabetes Couppé, Christian; Svensson, Rene Brüggebusch; Kongsgaard, Mads ...
Journal of applied physiology (1985),
2016-Jan-15, 2016-01-15, 20160115, Letnik:
120, Številka:
2
Journal Article
Recenzirano
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Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles ...tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between collagen glycation, Achilles tendon stiffness parameters, and plantar pressure in poorly (n = 22) and well (n = 22) controlled diabetic patients, including healthy age-matched (45-70 yr) controls (n = 11). There were no differences in any of the outcome parameters (collagen cross-linking or tendon stiffness) between patients with well-controlled and poorly controlled diabetes. The overall effect of diabetes was explored by collapsing the diabetes groups (DB) compared with the controls. Skin collagen cross-linking lysylpyridinoline, hydroxylysylpyridinoline (136%, 80%, P < 0.01) and pentosidine concentrations (55%, P < 0.05) were markedly greater in DB. Furthermore, Achilles tendon material stiffness was higher in DB (54%, P < 0.01). Notably, DB also demonstrated higher forefoot/rearfoot peak-plantar-pressure ratio (33%, P < 0.01). Overall, Achilles tendon material stiffness and skin connective tissue cross-linking were greater in diabetic patients compared with controls. The higher foot pressure indicates that material stiffness of tendon and other tissue (e.g., skin and joint capsule) may influence foot gait. The difference in foot pressure distribution may contribute to the development of foot ulcers in diabetic patients.
Charcot foot is a severe complication to diabetes mellitus, associated with diabetic neuropathy. Any long-term effects of a Charcot foot on the progress of neuropathy are still largely unexplored. ...The objective was to investigate whether a previous Charcot foot had any long-term effects on the progress of neuropathy.
An 8.5-year follow-up case-control study of 49 individuals with diabetes mellitus, 24 of whom also had Charcot foot at baseline visit in 2005-2007. Neuropathy was assessed with a questionnaire, biothesiometry, heart rate variability and venous occlusion plethysmography. Of the 49 baseline participants, 22 were able to participate in the follow-up. Twelve had passed away in the meantime. Heart rate variability was unchanged in both groups; from 9.7 to 7.2 beats/min (p = 0.053) in the Charcot group, and 14.3 to 12.6 beats/min (p = 0.762) in the control group. Somato-sensoric neuropathy showed no difference between baseline and follow-up in the Charcot group (from 39.1 to 38.5 V) (p = 0.946), but a significantly worsened sensitivity in the control group (from 25.1 to 38.9 V) (p = 0.002). In conclusion, we found that any differences in somatic or cardial autonomic neuropathy present at baseline had disappeared at follow-up after 8.5 years.
OBJECTIVE: To investigate the effect of flexible intensive insulin therapy (FIIT) and an automated bolus calculator (ABC) in a Danish type 1 diabetes population treated with multiple daily ...injections. Furthermore, to test the feasibility of teaching FIIT in a 3-h structured course. RESEARCH DESIGN AND METHODS: The BolusCal Study was a 16-week randomized, controlled, open-label, three-arm parallel, clinical study of 51 adults with type 1 diabetes. Patients aged 18–65 years in poor metabolic control (HbA1c 8.0–10.5%) were randomized to the Control (n = 8), CarbCount (n = 21), or CarbCountABC (n = 22) arm. During a 3-h group teaching, the Control arm received FIIT education excluding carbohydrate counting. CarbCount patients were taught FIIT and how to count carbohydrates. CarbCountABC group teaching included FIIT and carbohydrate counting and patients were provided with an ABC. RESULTS: At 16 weeks, the within-group change in HbA1c was –0.1% (95% CI –1.0 to 0.7%; P = 0.730) in the Control arm, –0.8% (–1.3 to –0.3%; P = 0.002) in the CarbCount arm, and –0.7% (–1.0 to –0.4%; P < 0.0001) in the CarbCountABC arm. The difference in change in HbA1c between CarbCount and CarbCountABC was insignificant. Adjusting for baseline HbA1c in a regression model, the relative change in HbA1c was –0.6% (–1.2 to 0.1%; P = 0.082) in CarbCount and –0.8% (–1.4 to –0.1%; P = 0.017) in CarbCountABC. Treatment satisfaction measured by the Diabetes Treatment Satisfaction Questionnaire (status version) improved in all study arms, but the improvement was significantly greater in CarbCountABC. CONCLUSIONS: FIIT and carbohydrate counting were successfully taught in 3 h and improved metabolic control and treatment satisfaction. Concurrent use of an ABC improved treatment satisfaction further.
A well-known metabolic side effect from treatment with glucocorticoids is glucocorticoid-induced diabetes mellitus (GIDM). Guidelines on the management of GIDM in hospitalized patients (in the ...non-critical care setting), recommend initiation of insulin therapy. The scientific basis and evidence for superiority of insulin therapy over other glucose lowering therapies is however poor and associated with episodes of both hypo- and hyperglycaemia. There is an unmet need for an easier, safe and convenient therapy for glucocorticoid-induced diabetes.
EANITIATE is a Danish, open, prospective, multicenter, randomized (1:1), parallel group study in patients with new-onset diabetes following treatment with glucocorticoids (> 20 mg equivalent prednisolone dose/day) with blinded endpoint evaluation (PROBE design). Included patients are randomized to either a Sodium-Glucose-Cotransporter 2 (SGLT2) inhibitor or neutral protamin Hagedorn (NPH) insulin and followed for 30 days. Blinded continuous glucose monitoring (CGM) will provide data for the primary endpoint (mean daily blood glucose) and on glucose fluctuations in the two treatment arms. Secondary endpoints are patient related outcomes, hypoglycaemia, means and measures of variation for all values and for time specific glucose values. This is a non-inferiority study with the intent to demonstrate that treatment with empagliflozin is not inferior to treatment with NPH insulin when it comes to glycemic control and side effects.
This novel approach to management of glucocorticoid-induced hyperglycemia has not been tested before and if SGLT2 inhibition with empaglifozin compared to NPH-insulin is a safe, effective and resource sparing treatment for GIDM, it has the potential to improve the situation for affected patients and have health economic benefits.
www.clinicaltrialsregister.eu no.: 2018-002640-82. Prospectively registered November 20th. 2018. Date of first patient enrolled: June 4th. 2019. This protocol article is based on the EANITATE protocol version 1.3, dated 29. January 2018.
Background. Charcot osteoarthropathy of the foot (COA) can currently only be treated using prolonged periods of immobilization of the affected extremity. Therefore, the hypothesis is that COA leads ...to altered body composition and increased sarcopenia. Objective. To investigate the changes over several years in sarcopenia, body composition, and fat distribution in diabetes patients with previous COA compared to diabetes patients without previous COA. Methods. Prospective observational clinical study. Twenty-one subjects were included and had two DXA scans done with mean 8.6-year intervals to compare changes in lean mass and fat distribution. The lean mass of limbs was used as an estimate of appendicular lean mass (aLM). Fat mass and aLM were then used to detect sarcopenic individuals using different methods. Results and Conclusions. As compared to baseline, both groups had significant loss of lean mass, and diabetics without COA had significant gain of total fat percentage. No statistically different prevalence of sarcopenia between the groups could be established. Likewise, no difference was found in total lean and fat mass changes. None of the groups had statistically significant changes of android fat distribution. As compared with published data on sarcopenia, people with diabetes might be more prone to sarcopenia than healthy individuals.
Charcot foot is a rare but severe complication to diabetes and peripheral neuropathy. It is still unclear if an acute Charcot foot has long-term effects on the bone metabolism. To investigate this, ...we conducted a follow-up study to examine if a previously acute Charcot foot has any long-term effects on bone mineral density (BMD) or local or systemic bone metabolism.
An 8.5-year follow-up case–control study of 44 individuals with diabetes mellitus, 24 of whom also had acute or chronic Charcot foot at the baseline visit in 2005–2007, who were followed up in 2015 with DXA scans and blood samples.
21 of the 44 baseline participants participated in the follow-up. There were no difference in the change in total hip BMD from baseline to follow-up in either the Charcot or the control group (p = 0.402 and 0.517), and no increased risk of osteoporosis in the previous Charcot feet either. From baseline to follow-up, there was a significant difference in the change in levels of fsRANK-L in the Charcot group, but not in the control group (p = 0.002 and 0.232, respectively). At follow-up, there were no differences in fsRANK-L between the groups. The fsRANK-L/OPG ratio also significantly decreased from baseline to follow-up in the Charcot group (3.4 versus 0.5) (p = 0.009), but not in the control group (1.3 versus 1.1) (p = 0.302).
We found that diabetes patients with an acute Charcot foot have an elevated fsRANK-L/OPG ratio, and that the level decreased from baseline to follow-up to be comparable to the level in diabetes patients without previous or current Charcot foot. We found no permanent effect of an acute Charcot foot on hip or foot BMD.
Objective. Due to the localized nature of Charcot foot, systemically altered levels of inflammation markers can be difficult to measure. The aim of this study was to investigate whether it is ...possible to detect an arteriovenous (A-V) flux in any locally produced inflammatory biomarkers from an acute Charcot foot by comparing local and systemic measurements. Methods. We included patients with acute diabetic Charcot foot. Blood was sampled from the vena saphena magna on the distal part of the crus bilaterally as well as from the arteria radialis. To minimize the A-V shunting effect, the feet were externally cooled with ice water prior to resampling. Results. Both before and after cooling, the A-V flux of interleukin-6 (IL-6) between the Charcot feet and the arterial level was significantly higher than the flux between the healthy feet and the arterial level (Δvaluebefore: 7.25 versus 0.41 pg/mL, resp., p=0.008; Δvalueafter: 10.04 versus 1.68 pg/mL, resp., p=0.032). There were no differences in the fluxes for other markers of inflammation. Conclusion. We have found an increased A-V flux of IL-6 in the acute diabetic Charcot foot compared to the healthy foot in the same patients.
Abstract Background Treatment of Charcot osteoarthropathy (COA) requires restricted walking and offloading for several months, which lead to fat re-distribution and increased sarcopenia. ...Objectives/Aim To investigate whether subjects with COA have an altered body composition compared to controls. Methods Cross-sectional case-control study of people with diabetes with acute or chronic Charcot osteoarthropathy, matched with otherwise healthy people with diabetes. A total of 49 subjects (distribution ~ 1:1) had a total body DXA-scanning, measuring appendicular lean mass, android/gynoid and truncal/total body fat distribution ratios. Results Sarcopenia frequency was higher in the total population with diabetes overall (9–40%), compared to normal materials. Using two different models for correlating appendicular lean mass to sarcopenia, there were no differences in sarcopenia-rates between the groups (P = 0.413 and 0.948 respectively). There was no significant difference in lean tissue mass between the affected and the unaffected leg in the immobilised subject group (P = 0.830). The average fat percentage was (29.4–37.7%) in the population with diabetes, compared to a matching background population (24.5–31.9%), whereas there were no significant differences found between the groups (P = 0.065). Neither truncal/total fat percent nor android/gynoid fat percent ratios showed differences between the groups. Conclusion To our knowledge, this is the first published dataset investigating body composition in subjects with Charcot osteoarthropathy. The study population of diabetics were more fat and sarcopenic than normal subjects, whereas no statistically significant impact of Charcot osteoarthropathy was found.
OBJECTIVE
To investigate the effect of flexible intensive insulin therapy (FIIT) and an automated bolus calculator (ABC) in a Danish type 1 diabetes population treated with multiple daily injections. ...Furthermore, to test the feasibility of teaching FIIT in a 3-h structured course.
RESEARCH DESIGN AND METHODS
The BolusCal Study was a 16-week randomized, controlled, open-label, three-arm parallel, clinical study of 51 adults with type 1 diabetes. Patients aged 18–65 years in poor metabolic control (HbA1c 8.0–10.5%) were randomized to the Control (n = 8), CarbCount (n = 21), or CarbCountABC (n = 22) arm. During a 3-h group teaching, the Control arm received FIIT education excluding carbohydrate counting. CarbCount patients were taught FIIT and how to count carbohydrates. CarbCountABC group teaching included FIIT and carbohydrate counting and patients were provided with an ABC.
RESULTS
At 16 weeks, the within-group change in HbA1c was −0.1% (95% CI −1.0 to 0.7%; P = 0.730) in the Control arm, −0.8% (−1.3 to −0.3%; P = 0.002) in the CarbCount arm, and −0.7% (−1.0 to −0.4%; P < 0.0001) in the CarbCountABC arm. The difference in change in HbA1c between CarbCount and CarbCountABC was insignificant. Adjusting for baseline HbA1c in a regression model, the relative change in HbA1c was −0.6% (−1.2 to 0.1%; P = 0.082) in CarbCount and −0.8% (−1.4 to −0.1%; P = 0.017) in CarbCountABC. Treatment satisfaction measured by the Diabetes Treatment Satisfaction Questionnaire (status version) improved in all study arms, but the improvement was significantly greater in CarbCountABC.
CONCLUSIONS
FIIT and carbohydrate counting were successfully taught in 3 h and improved metabolic control and treatment satisfaction. Concurrent use of an ABC improved treatment satisfaction further.
To investigate the effect of flexible intensive insulin therapy (FIIT) and an automated bolus calculator (ABC) in a Danish type 1 diabetes population treated with multiple daily injections. ...Furthermore, to test the feasibility of teaching FIIT in a 3-h structured course. The BolusCal Study was a 16-week randomized, controlled, open-label, three-arm parallel, clinical study of 51 adults with type 1 diabetes. Patients aged 18-65 years in poor metabolic control (HbAsub 1c 8.0-10.5%) were randomized to the Control (n = 8), CarbCount (n = 21), or CarbCountABC (n = 22) arm. During a 3-h group teaching, the Control arm received FIIT education excluding carbohydrate counting. CarbCount patients were taught FIIT and how to count carbohydrates. CarbCountABC group teaching included FIIT and carbohydrate counting and patients were provided with an ABC. At 16 weeks, the within-group change in HbAsub 1c was -0.1% (95% CI - 1.0 to 0.7%; P = 0.730) in the Control arm, -0.8% (-1.3 to -0.3%; P = 0.002) in the CarbCount arm, and -0.7% (-1.0 to -0.4%; P < 0.0001) in the CarbCountABC arm. The difference in change in HbAsub 1c between CarbCount and CarbCountABC was insignificant. Adjusting for baseline HbAsub 1c in a regression model, the relative change in HbAsub 1c was -0.6% (-1.2 to 0.1%; P = 0.082) in CarbCount and -0.8% (-1.4 to -0. 1%; P = 0.017) in CarbCountABC. Treatment satisfaction measured by the Diabetes Treatment Satisfaction Questionnaire (status version) improved in all study arms, but the improvement was significantly greater in CarbCountABC. FIIT and carbohydrate counting were successfully taught in 3 h and improved metabolic control and treatment satisfaction. Concurrent use of an ABC improved treatment satisfaction further. 23 references
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