Comparative characteristics of older people with type 1 diabetes treated with continuous subcutaneous insulin infusion or insulin injection therapy: data from the German/Austrian DPV registry.

AIM: To compare clinical characteristics and outcomes in adults with type 1 diabetes aged ≥ 60 years using continuous subcutaneous insulin infusion (CSII) vs. insulin injection therapy. Further, to determine the percentage of older adults with type 1 diabetes using CSII. RESEARCH DESIGN AND METHODS: Retrospective study using data of the Diabetes Prospective Follow-up Registry (DPV). Including percentage CSII use from 2008 to 2018, and the characteristics of 9547 individuals extracted from the DPV in March 2019 (N = 1404 CSII; N = 8143 insulin injection therapy). Wilcoxon rank sum tests were used for continuous variables and chi-square tests for categorical variables to compare clinical characteristics of people using CSII vs. insulin injection therapy. Adjusted analyses used generalized linear models to compare diabetes-related outcomes. RESULTS: CSII usage has increased in older adults (from 12% in 2008 to 23% in 2018). After adjustment, CSII was associated with lower HbA1c [60.7 mmol/mol (7.7 ± 0.1%) vs. 62.8% (7.9 ± 0.1%)], lower daily insulin dose (0.49 ± 0.02 vs. 0.61 ± 0.01 IU/kg), fewer days in hospital (8.1 ± 0.12 vs. 11.2 ± 0.11 days/person-year), fewer severe hypoglycaemic events (0.16 ± 0.02 vs. 0.21 ± 0.03 events/person-year) and fewer diabetic ketoacidosis (0.06 ± 0.01 vs. 0.08 ± 0.01 events/person-year). Individuals on CSII showed lower rates of microalbuminuria and also have a diagnosis of depression and neuropathy. CONCLUSIONS: A growing number of older adults are using insulin pumps. Older age in itself should not be seen as a contraindication for CSII.

Are insulin analogues detemir or glulisine used preferentially in overweight/obese subjects? A German multicentre analysis of 38560 type 2 diabetic patients from the DPV registry.

OBJECTIVE: Several studies suggest benefits of insulin analogues detemir or glulisine in overweight and obese patients with type 2 diabetes. The present multicentre study therefore examines, whether these insulin analogues are used more frequently in patients with increased body mass index. METHODS: Data of 38 560 adult type 2 diabetic patients using insulin analogues, from 150 centres in Germany, registered in a standardized, prospective, computer-based documentation program (DPV), were included. Patients were classified into body mass index categories according to World Health Organization. Analysis was stratified by 3 time periods. To adjust for confounding effects, multivariable logistic regression models were created. RESULTS: Detemir was preferentially used in overweight (OR 1.36, 95%-CI 1.20-1.53) and obese patients (OR 2.06, 95%-CI 1.84-2.31) compared to normal-weight patients. These effects remained significant after adjusting for sex, age, new/old federal state of Germany, size of centre, treatment in university clinic and clinic/specialized private practice. Models were additionally adjusted for time period and interaction of BMI category with age or sex. For glulisine, a minor effect was present when comparing obese to normal-weight patients (OR 1.26, 95%-CI 1.06-1.50). After adjustment, this finding was no longer significant. Stratified by obesity grade, class III obese patients more frequently used detemir or glulisine compared to class I obese patients. Comparing time periods, odds ratios did not differ, neither for detemir nor for glulisine. CONCLUSION: Detemir is used more often in overweight and obese patients compared to normal-weight patients. For glulisine, the relationship is less pronounced.

Is there a benefit to use calculated percent body fat or age- and gender-adjusted BMI-SDS(LMS) to predict risk factors for cardiovascular disease? A German/Austrian multicenter DPV-Wiss analysis on 42 048 type 2 diabetic patients.

OBJECTIVE: In clinical practice Body Mass Index is generally used to evaluate overweight status in adults. The present multicenter study examines whether Body Mass Index (BMI), age- and gender-adjusted Body Mass Index Standard Deviation Score, or calculated %body fat is a better predictor for cardiovascular disease risk factors, specifically hypertension and dyslipidemia, in a high-risk population. METHODS: Data of 42 048 adult type 2 diabetic patients (median age: 67.1 years) from 161 centers in Germany (n=158) and Austria (n=3) registered in a standardized, prospective, computer-based documentation program, were included in the study. For each patient body weight, height, blood pressure and blood lipids were documented. Spearman correlation analyses as well as multivariable logistic regression models were used to examine the relationship between anthropometric measurements and cardiovascular disease risk factors. RESULTS: Correlation and regression analyses revealed minor, non significant differences between the 3 anthropometric measurements (all p>0.05). In both genders, relationships between anthropometric measurements and hypertension or reduced HDL-cholesterol were nearly identical. Only for increased triglycerides, the relations with the 3 anthropometric measurements were significantly stronger in males than in females (p<0.0001, respectively). With increasing age, associations between anthropometric measurements and hypertension, reduced HDL-cholesterol or increased triglycerides became weaker. Spearman correlation coefficients for total cholesterol and LDL-cholesterol revealed weak associations with the 3 anthropometric measurements. CONCLUSION: Compared to Body Mass Index, age- and gender-adjusted Body Mass Index Standard Deviation Score, or calculation of %body fat, has no further benefit to predict cardiovascular disease risk factors in adult type 2 diabetic patients.

Healing times and prediction of wound healing in neuropathic diabetic foot ulcers: a prospective study.

Time line of wound healing and prediction of healing times in diabetic foot ulcers is an important issue. Usually, the percentage of wounds healed within a defined period is used for characterization of wound healing. R=sqrtA/pi (R, radius; A, planimetric wound area; pi, constant 3.14), and the wound radius reduction was 0.39 mm/week which was previously established. The initial average wound area was 96.9+/-13.1 mm2 (mean+/-SEM), and 3.61+/-1.6 mm 2 after ten weeks with an average healing time of 75.9 (95 %-CI 71-81) days. Using the equation mentioned above and the calculated weekly wound radius reduction, the predicted healing time in the test group was 86.9 (95 %-CI 73-101) days. The predicted and the observed healing times were significantly correlated with each other (r=0.55, p=0.0002). Providing standard care, the time needed for wound healing can reliably be predicted in neuropathic diabetic foot ulcers. This may be a useful tool in daily clinical practice to predict wound healing and recognize ulcers who do not respond adequately to the treatment.

The effects of ulcer size on the wound radius reductions and healing times in neuropathic diabetic foot ulcers.

The main problems in the treatment of diabetic foot ulcers are prolonged wound healing and not necessary amputations, which may sometimes be caused by the impression that the results of conservative treatment are somewhat unpredictable. The aim of this study was to determine the effects of ulcer size on the wound radius reduction and healing times using a previously established equation for wound healing in neuropathic diabetic foot ulcers. This prospective study evaluates wound healing in 120 diabetic patients with neuropathic foot ulcers who were grouped according to four different ulcer areas (A 100 150 200 mm (2)). Ulcer healing was assessed by planimetric measurement of the wound area every second week until wound healing. The time course of wound healing in the different groups was compared by the weekly wound radius reduction using the equation R = sqrt A/pi. The average healing time in group A was 70 (95 %-CI 64 - 77) days with a wound radius reduction of 0.42 mm/week (95 %-CI 0.28 - 0.56). In group B the average healing time was 79 (95 %-CI 75 - 82) days and the weekly wound radius reduction was 0.47 mm (95 %-CI 0.45 - 0.49). The average healing time in group C was 85 (95 %-CI 80 - 89) days with a wound radius reduction of 0.53 mm/week (95 %-CI 0.42 - 0.56). In group D the average healing time was 97 (95 %-CI 91 - 103) days. The weekly wound radius reduction was 0.57 mm (95 %-CI 0.49 - 0.81). Wound radius reductions and the time needed for healing are affected by the ulcer area, a measure of ulcer size, in neuropathic diabetic foot ulcers. The calculation of the weekly wound radius reduction for different ulcer areas may be a useful tool in daily clinical practice to identify ulcers who do not respond adequately to the treatment.

The effects of applied felted foam on wound healing and healing times in the therapy of neuropathic diabetic foot ulcers.

AIMS: The application of felted foam is a promising method for plantar pressure reduction in the ulcer region of diabetic foot ulcers, but knowledge of its effects on wound healing is sparse. The objective of this study was to evaluate the effects of felted foam on wound healing in diabetic foot ulcers compared with a standard method of plantar pressure relief. MATERIALS AND METHODS: A total of 54 Type 1 or Type 2 diabetic patients with neuropathic diabetic foot ulcers were evaluated in this prospective randomized controlled study. Ulcer healing was assessed by planimetric measurement of the wound area at beginning of the study and after 10 weeks and at least until wound healing. The patients were consecutively enrolled in the study; 24 patients were randomized to the felted foam therapy, and 30 patients were randomized to conventional therapy. RESULTS: In the felted foam group, the initial average wound area was 102.3 +/- 45.3 mm2 (mean +/- sd), and 5.4 +/- 3.1 mm2 after 10 weeks with an average healing time of 75 days [95% confidence interval (CI) 67-84]. In the conventional therapy group, the initial average wound area was 112.5 +/- 50.8 mm2, and 10.6 +/- 4.2 mm2 after 10 weeks with an average healing time of 85 days (95% CI 79-92) (P = 0.03). The mean wound radius decreased by 0.48 mm (95% CI 0.42-0.56) per week in the felted foam group and by 0.39 mm (95% CI 0.35-0.42) per week in the conventional group (P = 0.005). CONCLUSIONS: The felted foam technique appears to be at least as effective as conventional plantar ulcer treatment. It may be a useful alternative in treating neuropathic foot ulceration, especially in patients who are not able to avoid weight-bearing reliably.

Pitfall in diagnosing growth hormone deficiency in a hypochondroplastic patient with a delayed puberty.

Hypochondroplasia is a clinically and genetically heterogeneous skeletal dysplasia with less obvious disproportion in childhood and a reduced pubertal growth spurt. We report on a young hypochondroplastic man who had been misdiagnosed and treated as being growth hormone (GH) deficient in the early phase of puberty. The delay of his puberty which is unusual in hypochondroplasia might have confused the results of provocative GH testing. At the age of 17 years measurement of body proportions revealed an increased upper to lower body segment ratio. Skeletal radiographs showed a lack of increase in the interpedicular distance from the first to the fifth lumbar vertebra, anteroposterior shortening of the lumbar pedicles, short femoral necks, a fibula longer than the tibia, and short tubular bones. As the clinical and radiographic features suggested the diagnosis of a skeletal dysplasia, a DNA sequence analysis of the fibroblast growth factor receptor 3 gene on chromosome 4 p16.3 was performed, which identified the missense mutation C1620 G in the tyrosine kinase domain resulting in an Asn540Lys substitution. Hypochondroplastic children with this common mutation (N540K) were previously found to respond to GH treatment with an increase in sitting height compared to leg length, which accentuated the existing disproportion. We want to emphasise that in children with normal serum IGF-I and IGFBP-3 levels accurate measurements of body proportions and skeletal radiographs in disproportionate cases are more important than reiterative GH stimulation tests, which prepubertally and in the early phase of puberty often show subnormal responses.

Applied felted foam for plantar pressure relief is an efficient therapy in neuropathic diabetic foot ulcers.

The application of felted foam is a promising method for plantar pressure reduction in the ulcer region of neuropathic diabetic foot ulcers, but the knowledge of its impact on the wound healing and healing times in foot ulcers compared to conventional methods of pressure relief is sparse. The aim of this study was to assess the effects on the wound healing of felted foam dressings for plantar pressure reduction in the therapy of neuropathic foot ulcers. This prospective cohort study evaluates healing times and wound healing in 61 diabetic patients with neuropathic foot ulcerations. Ulcer healing was assessed by planimetric measurement of the wound area at beginning of the study and after 10 weeks and at least until wound healing. The patients were consecutively enrolled in the study, 27 patients were randomized to the felted foam therapy, and 34 patients were randomized to conventional therapy. In the felted foam group, the initial average wound area was 110.8 +/- 14.4 mm 2 (mean +/- SE), and 2.1 +/- 0.5 mm 2 after ten weeks (p < 0.0001), with an average healing time of 79.6 (95%-CI 75-84) days. In the conventional therapy group, the initial average wound area was 119.2 +/- 13.8 mm 2, and 3.4 +/- 0.7 mm 2 after ten weeks (p < 0.0001). The average healing times was 83.2 (95%-CI 77-90) days. Both with respect to the wound healing process and the healing times, the felted foam technique appears to be as effective as conventional plantar ulcer treatment. We conclude that the felted foam technique is an useful alternative in the therapy of the neuropathic diabetic foot syndrome, especially in patients who are not able to avoid weight-bearing reliably.

Early detection of microcirculatory impairment in diabetic patients with foot at risk.

OBJECTIVE: To assess microcirculatory impairment and alterations of the skin oxygen supply in diabetic patients with foot at risk. RESEARCH DESIGN AND METHODS: This study evaluated skin blood flow in 21 type 2 diabetic patients with a foot at risk (defined as a foot with neuropathy but without ulceration or previous ulcerations), 20 type 2 diabetic patients without foot lesions or neuropathy, and 21 normal subjects as a control group. The skin blood flow was determined by measuring the transcutaneous oxygen pressure (TcPO(2)) at the dorsum of the foot in supine and sitting position. The clinical assessment included standard measures of peripheral and autonomic neuropathy, but peripheral vascular disease was excluded by Doppler ultrasound. RESULTS: In supine position, TcPO(2) was significantly reduced (means +/- SE) in diabetic patients with foot at risk (6.04 +/- 0.52 kPa) compared with diabetic (7.14 +/- 0.43 kPa, P = 0.035) and nondiabetic (8.10 +/- 0.44 kPa, P = 0.01) control subjects. The sitting/supine TcPO(2) difference was higher in diabetic subjects with foot at risk (3.13 +/- 0.27 kPa) compared with both diabetic (2.00 +/- 0.18, P = 0.004) and nondiabetic (1.77 +/- 0.15 kPa, P = 0.0003) control subjects. The mean sitting/supine ratio was 1.70 +/- 0.12 in diabetic patients with foot at risk, 1.32 +/- 0.04 in diabetic control subjects, and 1.25 +/- 0.03 in nondiabetic control subjects (P = 0.007). The sitting/supine TcPO(2) ratio was negatively correlated with the heart rate variation coefficient at rest (r = -0.32, P = 0.044) and at deep respiration (r = -0.31, P = 0.046). CONCLUSIONS: Our data indicate that skin oxygen supply is reduced in type 2 diabetic patients with foot at risk. This is probably due to an impaired neurogenic blood flow regulation and may contribute to capillary hypertension, followed by disturbed endothelial function leading to edema and skin damage of the foot. The determination of TcPO(2) appears to be a useful tool in screening type 2 diabetic patients for foot at risk.

Metallothionein in isolated pancreatic islets of mice: induction by zinc and streptozotocin, a naturally occurring diabetogen.

Metallothionein (MT) concentrations were determined in the cytosol of isolated pancreatic islets of mice, using both the cadmium (Cd)-heme and the Cd-Chelex assay. Both constitutive MT levels and significant MT induction were detected in islet cells. For MT induction, mice were injected intraperitoneally (i.p.) with either zinc sulfate (Zn) or the diabetogen streptozotocin (STZ). Following an i.p. injection of 15 mg Zn.kg-1 body weight (body wt), the mean index of MT induction found in islets was comparable to that found in liver tissue, which was used as control. After i.p. injection of 30 mg Zn.kg-1 or a single high dose of STZ (100 or 200 mg.kg-1), the indices of MT induction in islets exceeded those in liver by a factor of 1.3, 2.5, or 1.5. After multiple low doses of STZ (3 or 5 x 40 mg.kg-1 given on consecutive days), in contrast, the MT induction indices in islets exceeded those in liver by a factor of 3.5 and 3.9 for 3 x 40 respectively 5 x 40 mg STZ.kg-1. In conclusion, our results demonstrate constitutive MT levels in isolated pancreatic islets and significant MT induction after i.p. injection with Zn or STZ, in particular after repeated low doses of STZ.