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The article examines the decreasing incidence rates of lower extremity amputations (LEA) among diabetes patients in Denmark and highlights the need for further reductions. Topics discussed include the regional disparities in amputation rates, the impact of improved treatment and patient education on reducing LEA, and the importance of preventive foot examinations in diabetes care.

Introduction: Little is known about treatment of osteoporosis with denosumab (Prolia®) in patients with decreased kidney function. The aim of this retrospective case report study was to investigate effects and side-effects of such treatment. Methods: Since 2012, 75 patients with osteoporosis and decreased kidney function had been treated with denosumab (Prolia®) in the osteoporosis outpatient clinic of the department of endocrinology, Bispebjerg Hospital, University of Copenhagen, Denmark, and data were retrospectively collected from the patient records of these patients in 2021. Results: At baseline, the mean estimated glomerular filtration rate (eGFR) was 34 mL/min (range 9–50) and the median age was 85 years (range 45–103). 95% of the patients had had low-energy fractures, and the bone mineral density T score of the hips was on average − 2.7. All, but one, patients had normal/high parathyroid hormone (PTH) levels. The mean duration of the treatment with denosumab at the follow-up was 5.3 years (range 1.5–10). There was an annual increase of 12% and of 7% in the T score of in the lumbar spine and hip, respectively, compared to the T-scores prior to the denosumab treatment. 20% had a new fracture during the follow-up. 21% had biochemical hypocalcemia following denosumab injection, 7% developed symptoms of hypocalcemia, whereas 4% needed to be hospitalized acutely. Conclusion: Treatment with denosumab of osteoporosis in patients with decreased kidney function (eGFR 9–50 mL/min), with normal/high PTH, seems in general to be well tolerated, with improvement of bone and decreased risk of new fractures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Charcot foot is a rare complication to neuropathy and can cause severe foot deformities and ulcerations, which often require prolonged antibiotical treatment. The objective of this retrospective study was to investigate whether this treatment is associated to impaired renal function. Results: In total, 163 patients were included, of whom 105 (64%) had received β-lactam antibiotics for a mean total duration of 13.0 months. There was a significant increase in the urine albumin/creatinine ratio in the group that received antibiotics (p = 0.017), and the use of antibiotics was associated to a subsequent diagnosis of nephropathy (p = 0.01). Patients treated with antibiotics had a 21.9% risk of developing subsequent nephropathy versus 5.2% for patients not treated with antibiotics. We suggest increased awareness on signs of nephropathy in patients with severe Charcot foot. [ABSTRACT FROM AUTHOR]

Objective: Charcot foot is a serious complication of diabetes, with degeneration of the bones and joints in the foot and ankle. It is unknown whether patients with diabetes with a Charcot foot have an increased risk of osteoporosis and fractures. The aim of this study was to investigate whether patients with diabetes with a Charcot foot have an increased risk of fracture and/or osteoporosis compared with patients with diabetes without Charcot foot.Research Design and Methods: A Danish register-based, nationwide population-based matched cohort study was conducted. During 1995-2018, we identified 1,602 patients with diabetes with Charcot foot and matched them on sex and date of diagnosis of diabetes with 16,296 patients with diabetes without Charcot foot. We used logistic regression to estimate odds ratios (ORs) with 95% CIs for fracture and osteoporosis. Information about exposure, outcome, and comorbidities was retrieved from the Danish National Patient Register.Results: Diabetes patients with Charcot foot had higher risk of fractures compared with those without Charcot foot (i.e., ORs for any fracture, lower-leg fracture, foot fracture, and osteoporotic fracture were 1.8 [95% CI 1.6-2.0], 2.4 [2.0-2.8], 2.9 [2.6-3.3], and 1.3 [1.1-1.4], respectively). Furthermore, patients with diabetes with Charcot foot had higher risk of osteoporosis compared with the patients without Charcot foot, with an OR of 1.3 (95% CI 1.1-1.5).Conclusions: Patients with diabetes with a Charcot foot have an increased risk of fractures and osteoporosis compared with patients with diabetes without a Charcot foot. [ABSTRACT FROM AUTHOR]

Aim. To describe differences in healing time of diabetic foot ulcers for patients treated at the Copenhagen Wound Healing Center, Bispebjerg Hospital, between the years 1999/2000 and 2011/2012. The Center is highly specialized and receives diabetes patients with hard-to-heal foot ulcers. A further aim is to attempt to find predictors of healing time of diabetic foot ulcers. Methods. A retrospective descriptive study of records from patients with diabetic foot ulcer treated at the Copenhagen Wound Healing Center in 1999, 2000, 2011, or 2012. Follow-up data was collected until the 3rd of August 2018. Results. Median time (range) to healing was 6 (61.3) months in 1999/2000 and 6.6 (67.8) in 2011/2012 (p=0.2). About 33% of ulcers were healed, 17% were minor or major amputated, and 1.5% were dead within one year in 1999/2000, whereas 30% of ulcers were healed (p=0.6), 14% were amputated (p=0.2), and 12.8% were dead within one year in 2011/2012 (p<0.001). The single factor found significantly associated with longer ulcer duration was infection. Related to shorter ulcer duration were toe localization of the ulcer and good glycemic control. Conclusion. The median time to healing of a diabetic foot ulcer was long, around 6 months and with a high recurrence rate in 1999/2000 as well as in 2011/2012. Some factors were found to be significantly related to healing time, and intervention addressing these may improve the time to heal, although such interpretations must be taken with precaution from the present study and should be proven in randomized prospective intervention trials. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Aim: To identify risk factors for early death in diabetes patients who undergo amputations below the ankle. Methods: A retrospective study, where all hospital records of all diabetes patients who had undergone minimum one amputation below the ankle at the CWHC Bispebjerg Hospital, Denmark, in the period 1996-2013, were examined. The amputations were mainly trans-metatarsal amputations and partial amputations of toes. The participants were found via ICD10- codes. The included patients were followed from their first contact to the last registered contact. The statistical analysis in this article is performed on patients with a of minimum 5-year follow-up. Results: The 5 year mortality was 42 % for patients with type 2 diabetes, and 29 % for patients with type 1 diabetes. For patients with type 2 diabetes, multivariable analysis showed that high age, peripheral arterial insufficiency and short time from first admission to amputation were independently statistically significantly associated with increased 5-years mortality. Use of statins was associated with decreased mortality. 35 % died as a result of their diabetes, mostly due to cardiovascular causes. Conclusion: Short time from first admission to amputation is a risk factor for early death. Arterial insufficiency and high age is also associated with increased mortality, whereas use of statin is associated with decreased mortality, in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article offers information on how common is the Rare Charcot Foot in patients with diabetes. Topics include Danish National Patient Register contains information on all hospitalizations and information on outpatient visits and emergency room contacts from 1995 to present, and the data about age, sex, and emigrations were retrieved from The Danish Civil Registration System, and dates of death were found in the Death Register.

BACKGROUND: Treatment of patients with perioxisome proliferator-activated receptor-[gamma] full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-[gamma] agonists has not been established in a clinical trial. The BALaglitazone glucose Lowering Efficacy Trial aimed to establish the glucose-lowering effects and safety parameters of the perioxisome proliferator-activated receptor-[gamma] partial agonist balaglitazone in diabetic patients on stable insulin therapy. METHODS: Four hundred and nine subjects from three countries with type 2 diabetes on stable insulin therapy were randomized to 26 weeks of double-blind treatment with once daily doses of 10 or 20 mg balaglitazone, 45 mg pioglitazone, or matching placebo (n >= 99 in each group). The primary endpoint was the efficacy of balaglitazone 10 and 20 mg versus placebo on the absolute change in haemoglobin A(1c) . Secondary endpoints included levels of fasting serum glucose, and changes in body composition and bone mineral density as measured by dual energy X-ray absorptiometry, in comparison to pioglitazone 45 mg. This study is registered with Clinicaltrials.gov identifier: NCT00515632. RESULTS: In the 10- and 20-mg balaglitazone groups, and in the 45-mg pioglitazone group, significant reductions in haemoglobin A(1c) levels were observed (-0.99, -1.11, and -1.22%, respectively; p < 0.0001) versus placebo. Fasting serum glucose was similarly reduced in all treatment arms. Dual energy X-ray absorptiometry analyses showed that, while balaglitazone at 10 mg caused weight gain and fluid retention compared to placebo, the magnitude of these effects was significantly smaller than that of pioglitazone 45 mg and balaglitazone 20mg. Balaglitazone at either dose did not appear to reduce bone mineral density, while Pioglitazone showed a trend towards a reduction. CONCLUSION: Patients treated with balaglitazone at 10 mg and 20 mg and pioglitazone at 45 mg showed clinically meaningful improvements in glucose levels and HbA(1c) . With the 10 mg dose, the benefits (glucose & HgA(1c) lowering) and untoward effects (fluid and fat accumulation) were less, results that encourage further studies of this drug candidate. [ABSTRACT FROM AUTHOR]

Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood-onset (CO) GHD, 18 years after stopping GH treatment.Twenty-six (11 females) patients with idiopathic CO GHD participated. All patients but two had been treated for isolated GHD in childhood. The childhood diagnosis was established by an insulin tolerance test (ITT) and reassessed in adulthood by an ITT (N = 21) or arginine test (n = 5), revealing that 10 patients had GHD according to adult criteria. Accordingly, the patient group was divided into (1) patients who did not have persistent GHD in adulthood and (2) patients who did have persistent adult GHD. Twenty-six healthy subjects acted as age-, gender- and body mass index (BMI)-matched controls.The patients who did not have persistent GHD had significantly lower IGF-I values and whole-body, femoral neck and lumbar spine BMD compared to controls[0·994 ± 0·10vs. 1·114 ± 0·11 g/cm2 (P = 0·003), 0·842 ± 0·12vs. 0·962 ± 0·11 g/cm2 (P = 0·006) and 1·026 ± 0·14vs. 1·127 ± 0·13 g/cm2 (P = 0·004), respectively]. Femoral neck BMD was significantly reduced in the patients who had persistent GHD, compared to controls (0·842 ± 0·09vs. 0·938 ± 0·11,P = 0·04). Significant correlations were observed between all bone variables and IGF-I in all subjects, whereas no correlations were observed between bone variables and GH peak levels in the 26 patients.In conclusion, we found that (1) patients with idiopathic CO GHD, who at retest in adulthood did not have GHD according to adult criteria, had reduced serum IGF-I and BMD/BMC compared to controls. (2) This observation was also made in the patients who did have persistent GHD in adulthood. The findings may reflect the fact that the present diagnostic criteria for adult GHD (i.e. response to the ITT) do not reflect the clinical consequences of disordered GH–IGF axis in CO GHD young adults who were treated with GH in childhood. Alternatively, despite seemingly adequate GH treatment in childhood an optimal peak bone mass in adolescence may never have been reached in either of the groups. (3) IGF-I levels correlated with clinical signs of the adult GHD syndrome. We believe that further studies on the indications and diagnostic procedures for GH treatment after cessation of linear growth are necessary. [ABSTRACT FROM AUTHOR]

Weight loss seems associated with a decrease in bone mineral density (BMD) as measured by absorptiometry, which may be the result of accuracy errors caused by differences in soft tissue between non-bone and bone pixels. The aim was to study the abdominal fat% and thickness in regions corresponding to non-bone, soft tissue-only and bone pixels for spinal BMD measurements by dual energy X-ray absorptiometry (DXA), and to calculate the theoretical errors in measurement of changes in BMD by DXA as a result of changes in soft tissue heterogeneity with weight loss. Abdominal computed tomography (CT) and DXA scans were performed in 34 obese subjects (42·1 ± 10·1 years (mean ± SD), wt: 102·1 ± 12·8 kg and BMI: 36·6 ± 3·8 kg m–2 ) before and after weight loss (11·3 ± 6·9 kg after 1 year). There were some significant differences in fat% and thickness of soft tissue between abdominal regions corresponding to non-bone and bone pixels, respectively, for spinal BMD measurements by DXA, both before and after weight loss. With weight loss there were some changes in the soft tissue heterogeneity, which caused a minor theoretical error (apparent, but false decrease of 1–2%) of borderline significance for the anterior–posterior (AP) spinal BMD by DXA. [ABSTRACT FROM AUTHOR]

The accuracy of body-composition measurements in vivo by dual-energy x-ray absorptiometry (DEXA) was assessed in seven pigs (weight: 35-95 kg) by measurement by DEXA in vivo and chemical analysis after postmortem homogenization. The regression lines between these measurements were not significantly different from the line of identity (P > 0.05), the r values were > 0.97, and the corresponding SEEs were 2.9%, 1.9 kg, and 2.7 kg for percent fat, fat tissue mass, and lean body mass, respectively. Changes in fat and lean tissue mass (simulated by placing 8.8 kg porcine lard on the trunk of six women) were accurately measured by DEXA. The measured total-body bone mineral (TBBM) was significantly affected by the lard (P < 0.05). In conclusion, DEXA is an accurate method for measurement of soft-tissue body composition. TBBM measurements in longitudinal studies may, however, be difficult to interpret if considerable change in soft-tissue composition has occurred. [ABSTRACT FROM AUTHOR]

The study compared measurements of resting energy expenditure (REE) by two methods, namely the commercially available ventilated canopy (Medgraphics CCM system) and the respiration chamber. Thirty-five healthy subjects of both sexes with a wide weight range (BMI 18–33·8 kg m[sup -2]) were measured on both systems. The linear regression equation was REE[sub canopy]=0·66 × REE[sub resp.cham.] + 61·1 (kJ h[sup -1]), and the corresponding SEE% was 8·6%. The correlation was high (r=0·89). However, the mean REE measured using the ventilated canopy was 41 kJ h[sup -1] (13%) lower than that using the respiration chamber (P<0·01). The Medgraphics CCM canopy system seems valid for measurements of REE. However, the REE results measured by the canopy were systematically lower than when measured by the respiration chamber, but can be converted by the equation given with an accuracy error of 9%. [ABSTRACT FROM AUTHOR]