The Diabetic Foot in a Multidisciplinary Team Setting. Number of Amputations below Ankle Level and Mortality.

Aim: To describe the number of minor lower extremity amputations and mortality for diabetes patients treated by a specialized multidisciplinary foot care team. Methods: A retrospective descriptive study of medical records from patients with diabetes treated with minor amputations at the Copenhagen Wound Healing Center (CWHC) at Bispebjerg Hospital from 1996-2013. Results: 777 diabetes patients treated with minor amputations were included. 77% were males and 23% were females. 80% had T2 diabetes and 20% had T1 diabetes. 89% of the patients had a foot ulcer at first contact. There was a total of 1 231 minor amputations. The amputations were mainly trans-metatarsal amputations and partial amputations of toes. There was an increase in the number of minor amputations, but there was also an increase in the number of referred diabetes patients, thus the ratio of amputations per admitted diabetes patient was constant. Time from first amputation to death was 2.5 years. The 5-year mortality rate was 43% and 52% for T1 and T2 diabetes patients, respectively. Conclusion: Due to increased number of referred diabetes patients, the number of diabetes patients undergoing minor amputations increased over the years. Patients with diabetes, who underwent minor amputation, had a high mortality averaging 2.5 year to death; comparable to many types of cancer.

Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function?

The aim of the study is to determine if attenuation of postprandial hyperglycemia, by acutely and chronically enhancing postprandial insulin secretion in insulin-resistant individuals, improves the endothelial dysfunction. We assessed postoral glucose-load endothelial function in 56 insulin-resistant subjects with the Flow-Mediated-Dilation (FMD) technique. We randomized subjects to intervention/control group, and examined the acute and chronic effect of nateglinide, an oral antidiabetic drug of rapid action. In the intervention group, postoral glucose-load (post-OGL) FMD delta values deteriorated when compared to pre-OGL values, most significantly at 3 h post-OGL, on the following days: on the first study day termed "Baseline day" (p=0.04); on both days after 3 months of nateglinide treatment [with nateglinide administered on study-day "acute+chronic" (p=0.01); and without nateglinide on study-day "Closing day", p=0.001]. Post-OGL changes in the control group were nonsignificant both at Baseline and on Closing day. After a single dose of nateglinide "Acute day", post-OGL FMD deterioration was abolished. There was an increment in post-OGL FMD delta values most significant at 2 h post-OGL (p=0.02). Insulin concentrations increased while glucose concentrations decreased on study-days with nateglinide when compared to study-days without (p=<0.001 for both insulin and glucose). Comparisons for insulin and glucose concentrations between days with nateglinide, and likewise between days without, showed no significant difference. Postglucose load endothelial dysfunction can be prevented by administration of nateglinide, however, after 3 months of nateglinide treatment, this effect is abolished. Chronically increased insulin secretion could counteract the initial beneficial effect of reduced glucose excursions. We found no relationship between postprandial hyperglycemia and post-OGL FMD.

Effects of oral glucose load on endothelial function and on insulin and glucose fluctuations in healthy individuals.

BACKGROUND/AIMS: Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied by endothelial dysfunction. We studied the effect of oral glucose load on insulin and glucose fluctuations, and on postprandial endothelial function in healthy individuals in order to better understand and cope with the postprandial state in insulin resistant individuals. METHODS: We assessed post-oral glucose load endothelial function (flow mediated dilation), plasma insulin, and blood glucose in 9 healthy subjects. RESULTS: The largest increases in delta FMD values (fasting FMD value subtracted from postprandial FMD value) occurred at 3 hours after both glucose or placebo load, respectively: 4.80 +/- 1.41 (P = .009) and 2.34 +/- 1.47 (P = .15). Glucose and insulin concentrations achieved maximum peaks at one hour post-glucose load. CONCLUSION: Oral glucose load does not induce endothelial dysfunction in healthy individuals with mean insulin and glucose values of 5.6 mmol/L and 27.2 mmol/L, respectively, 2 hours after glucose load.

Should measurement of body composition influence therapy for obesity?

This paper presents a review on assessment of obesity by measurement of body composition. It is recommended that cross-calibrations between methods are made and that cut-off levels for defining obesity are based on the association between body fat% and morbidity and mortality. The recommendation is made for assessment of obesity to measure body mass index (BMI) and waist circumference in combination with clinical judgment and a disease risk assessment. Assessment of body composition for evaluation of obesity is a valuable tool in research, but currently it does not influence the choice of therapy in an obese individual. An individual who is misclassified by BMI may benefit from measurement of body composition, but not until further evidence and development of current body composition methods are available.

Comparisons of leptin, incretins and body composition in obese and lean patients with hypopituitarism and healthy individuals.

OBJECTIVE: To identify possible abnormalities specific for obesity in hypopituitary patients. STUDY DESIGN: Cross-sectional case-control study. MEASUREMENTS AND STUDY SUBJECTS: Body composition (DEXA) and measurements of fasting plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptides (GLPs), insulin, C-peptide, glucose, leptin and lipids were performed in 25 hypopituitary patients (15 obese, 10 normal weight) and 26 BMI and age-matched healthy controls (16 obese, 10 normal weight). All hypopituitary patients had GH deficiency and received adequate substitution therapy on this and other deficient axes (3 +/- 1). RESULTS: Fasting GIP-levels were significantly higher in obese hypopituitary patients compared to lean hypopituitary patients (P < 0.01), while the fasting concentrations of GLP-1 and GLP-2 were comparable between obese and lean hypopituitary patients. The same trend was seen in obese healthy controls vs. lean controls. No differences were observed in glucose, insulin or C-peptide between the hypopituitary patients and the controls. Leptin levels were increased in obese hypopituitary patients compared to lean hypopituitary patients when adjusted for gender. At least a 2-fold higher level of leptin was observed in women compared to men in both patient groups and healthy controls. Lean female hypopituitary patients had higher leptin levels than matched controls. CONCLUSIONS: Fasting levels of GIP were elevated in obese substituted hypopituitary patients, while fasting concentrations of GLPs were similar. Obese hypopituitary patients had the same degree of hyperinsulinaemia, affected glucose tolerance, dyslipoproteinaemia and central obesity as obese healthy controls. Further studies are required to identify the possible biochemical reasons for obesity in patients with apparently well-substituted hypopituitarism.

Body composition in italian and Danish women.

The objective of this cross-sectional study was to compare the body composition and fat distribution measured by dual energy X-ray absorptiometry (DPX, Lunar) in different age decades of age-matched Danish and Italian women. The subjects comprised 133 healthy Italian women (age 20-60 years) age-matched to a representative sub-sample of healthy Danish women (n=375). Total and abdominal body fat tissue mass were measured by dual-energy X-ray absorptiometry. Italian women were shorter and fatter compared with age-matched Danish women, but in middle-age, had a less abdominal fat distribution. There was no difference in total body bone mineral density.

Measurements of body composition by dual-energy X-ray absorptiometry improve prediction of energy expenditure.

The prediction of energy expenditure by dual-energy X-ray absorptiometry (DXA) and bioimpedance analysis (BIA) was assessed in 35 healthy individuals of both sexes, with a mean body mass index (BMI) of 23.8 kg/m2 (range 18-33.8), and mean age of 30 years (22-40). Energy expenditure (EE) was measured under standard conditions in a respiration chamber, the total and regional body composition by DXA, and total body composition by BIA. When body composition was measured by BIA, 88.5% of the variation in 24-h EE was explained by lean body mass (LBM); this figure was increased by DXA, where total lean tissue mass (LTM) and total fat tissue mass (FTM) could account for 91.5% of the variation. Also, the prediction of resting energy expenditure (REE) was improved by DXA, from 88.1% to 89.8% (LBM vs. LTM, FTM). Measurements of regional body composition showed that trunk LTM was significantly superior as a predictor, especially of REE and sleeping EE (EE sleep), compared to the peripheral LTM; thus, the predictions of REE were 83% vs. 87% (peripheral vs. trunk), respectively; and the predictions of EE sleep were 83% vs. 89% (peripheral vs. trunk), respectively. Therefore, body composition measurements by DXA improved the prediction of EE. Trunk LTM was a superior predictor, especially of REE and EE sleep, compared to peripheral LTM. In conclusion, the present results suggest that measuring total and regional body composition by DXA can somewhat improve the prediction of EE.

The influence of long-term supplementation with biotin on the prevention of lameness in pasture fed dairy cows.

In a double-blind study, the influence of biotin supplementation on lameness in dairy cows was investigated over a 13-mo period. The experimental site was a tropical upland environment and involved over 2705 Holstein and Friesian cows on 20 participating farms. Cows on 10 farms received biotin at a rate of 20 mg/head per day in the concentrate, and cows on 10 other farms received feed without the biotin supplement. Premixes with or without biotin were incorporated into a grain concentrate that was fed at a constant rate to cows at milking. Farmers maintained accurate records of the nature of hoof problems and any treatment applied. Each herd was evaluated for locomotion scores at 8-wk intervals. Locomotion scores were significantly correlated with the number of days with measurable rainfall per month (r = 0.88). The biotin-supplemented herds exhibited better locomotion scores than the unsupplemented herds. In the wet summer period the number of lame cows, as observed by the farmer, were significantly fewer during the rainy period for the biotin-supplemented herds and required fewer antibiotic treatments than unsupplemented herds. Most hoof lesions were most commonly observed in the outer claws of the hind limb. Daily milk production (17.3 vs. 18.5 L) was not affected by biotin supplementation. Reduced milk fat percentage and somatic cell counts of bulk milk were recorded in the biotin supplemented herds during the wet, summer period.

Comparison of resting energy expenditure measurements by ventilated canopy and by respiration chamber.

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-2) were measured on both systems. The linear regression equation was REEcanopy = 0.66 x REEresp.cham. + 61.1 (kJ h-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-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%.

Does paracentesis of ascites influence measurements of bone mineral or body composition by dual-energy x-ray absorptiometry?

Measurements of bone mineral content (BMO) and density (BMD) by dual-energy x-ray absorptiometry (DXA) may be affected by changes in soft tissue overlying bone. Furthermore, the accuracy error for body composition determined by DXA may be high in the trunk region due to the complex bone geometry. Our objective was to evaluate the impact of paracentesis on measurements of bone mineral and body composition by DXA. DXA (Norland XR-36; Norland, Fort Atkinson, WI) scans were performed in six patients with cirrhosis of the liver before and after treatment of ascites by paracentesis. There were no significant differences in the spinal BMC (change [delta] = 0.04%) and BMD (delta = -0.9%) (P > .05), nor in total body BMC ([TBBMC] delta = 1.9%) and BMD ([TBBMD] delta = 0.4%) (P > .05). The median volume of ascites drained (6.8 L; range, 1.6 to 14.7) was not significantly different from the median change in total (5.8 kg; range, 2.0 to 16.1) or trunk lean tissue mass ([LTM] 5.8 kg; range, 1.9 to 11.9) (P > .05). The changes in body weight correlated with the changes in trunk LTM (r = .93, standard error of the estimate [SEE] = 1.8 kg, P = .007). Total and regional fat mass were not changed significantly by the paracentesis. We conclude that measurements of total body and spinal bone mineral by DXA are unaffected by large changes in the soft tissue composition and height of the trunk. Furthermore, the change in body composition induced by ascites drainage was accurately determined as a change in total body and trunk LTM on a group level.

Bone mineral in pre- and postmenopausal women with insulin-dependent and non-insulin-dependent diabetes mellitus.

The aim of the study was to compare bone mineral density (BMD) and bone turnover in pre- and postmenopausal women with insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM) and normal reference women. In a cross-sectional study 31 and 11 premenopausal and 22 and 21 postmenopausal IDDM and NIDDM patients, respectively, were recruited from an outpatient clinic. BMD in the forearm, spine, femur and total body and biochemical markers of bone turnover were measured and compared with reference values obtained from measurements of normal healthy pre- and postmenopausal women. Postmenopausally, but not premenopausally, IDDM patients had lower BMD values than NIDDM patients. Postmenopausal NIDDM patients had higher BMD value than normal women. The differences in BMD between IDDM and NIDDM patients could be explained statistically by differences in body weight between the NIDMM (obese) and IDDM (lean) women. Markers of bone turnover were significantly higher postmenopausally than premenopausally in both IDDM and NIDDM patients. Osteocalcin was significantly lower in postmenopausal NIDDM compared with postmenopausal IDDM patients and reference values. Otherwise there were no differences in the markers of bone turnover between NIDDM and IDDM patients. In conclusion, postmenopausal IDDM patients have a relatively decreased BMD, whereas NIDDM patients seem to be relatively protected from postmenopausal bone loss.

Leptin in overweight postmenopausal women: no relationship with metabolic syndrome X or effect of exercise in addition to diet.

OBJECTIVE: To examine the effect of diet with exercise on serum leptin and whether leptin is associated with the metabolic syndrome X in a high risk population such as overweight postmenopausal women. STUDY DESIGN AND SUBJECTS: 121 healthy overweight, postmenopausal women (aged 49-58y, body mass index (BMI) 25-42 kg/m2) were randomized to: A low-energy-diet, 4.2 MJ/d (n = 51), low-energy-diet + standardized physical exercise (n=49) or no intervention (control: n=21) for 12 weeks, followed by 6 months follow-up without intervention. MEASUREMENTS: S-leptin was measured by Radio Immuno Assay (RIA), body composition and fat distribution by dual energy X-ray absorptiometry (DEXA) and anthropometry. Factors associated with the metabolic syndrome X and sex hormones were measured. RESULTS: S-leptin was two-fold higher than in normal-weight postmenopausal women and S-leptin was normalized after weight loss induced by the 12-week low-energy-diet, without any additive effect of the exercise. Of the factors associated with the metabolic syndrome X, serum-leptin correlated significantly only with sex-hormone-binding-globulin and plasminogen-activator-inhibitor-1, whereas factors associated with obesity per se correlated significantly with leptin. Changes in S-leptin correlated with changes in fat tissue mass during the follow-up, but not during the intervention. S-leptin at baseline did not correlate with either short term or long term weight loss. CONCLUSION: There is no effect of exercise added to diet on S-leptin in overweight postmenopausal women. Leptin does not seem to be associated with the metabolic syndrome X, but rather with fatness. S-leptin is probably associated with both dynamic and static effects of adipose tissue. S-leptin did not predict weight loss.

Body composition and fat distribution measured by dual-energy x-ray absorptiometry in premenopausal and postmenopausal insulin-dependent and non-insulin-dependent diabetes mellitus patients.

The study aim was to measure body composition and fat distribution in premenopausal and postmenopausal women with insulin-dependent ([IDDM] n = 53) and non-insulin-dependent ([NIDDM] n = 32) diabetes mellitus by dual-energy x-ray absorptiometry. IDDM and NIDDM patients had similar, normal lean tissue mass (LTM) and 24-hour urinary excretion of creatinine. Total body and abdominal fat percentages were higher in the NIDDM group (approximately 40%) than in the IDDM group (-27%, P < .001) and were constant with age and menopausal status in both groups. In postmenopausal patients with IDDM, total body and abdominal fat values were less than in postmenopausal healthy women (approximately 27% v approximately 37%, P < .001). In premenopausal patients with NIDDM, total body and abdominal fat were higher than in premenopausal healthy women (approximately 42% v approximately 25%, P < .001). In conclusion, women with IDDM or NIDDM have a normal LTM and probably a normal muscle mass. Total body and abdominal fat were higher for women with NIDDM than for those with IDDM.

Body composition analysis by dual energy X-ray absorptiometry in female diabetics differ between manufacturers.

OBJECTIVE: Comparison of body composition results by two dual energy X-ray absorptiometry (DXA) instruments, namely QDR-2000 from Hologic Inc and from Lunar in subpopulations of lean and obese subjects. DESIGN: Cross-sectional study with 85 female diabetics (BMI 18-43 kg/m2) measured with both DXA instruments. RESULTS: The regression lines for fat tissue mass (FTM), FAT% and total body bone mineral content (TBMC), but not lean tissue mass (LTM), were different from the line of identity (P < 0.01). However, the relationships were high (r2 > 0.95), and the corresponding SEE%'s were low (0.8-4.8%), and were independent of BMI. FTM and FAT% measured by the QDR-2000 were 10% higher, and LTM and TBMC 6% lower, than by DPX (P < 0.001). CONCLUSIONS: There were lack of agreements between total body composition results by DPX Lunar, and QDR-2000 Hologic Inc. Individual results on the two systems cannot be directly compared. Standardization of body composition measurements by DXA is strongly needed.

[Significance of intentional weight loss on health]. / Den sundhedsmaessige betydning af tilsigtet vaegttab.

The aim of the present study was critically to review how intentional weight loss in overweight and obesity influences mortality. No randomized weight loss intervention trial has included mortality as an end-point. However, even minor weight loss causes beneficial changes in risk factors for cardiovascular disease, whereas the vast majority of observational studies have linked weight loss to excess mortality. Most observational studies do not have information on intentionality of weight loss and suffer from other methodological limitations making inferences from these studies difficult. Given the available observational evidence, the possibility that intended weight loss may cause some increased mortality cannot be excluded. However, considering the totality of the evidence on effects of intended weight loss among overweight and obese subjects, there may be other benefits, such as: psycho-social and physical well-being, risk factor improvement, decreased morbidity, and in certain high-risk subgroups decreased mortality. Treatment of obesity is therefore recommended, particularly in the presence of risk factors or complications.

Effects on muscle of dieting with or without exercise in overweight postmenopausal women.

The main aim of this study was to investigate the effect of an energy-restrictive, high-protein diet with or without exercise on muscle morphology and biochemistry. Moderately overweight postmenopausal women (49-58 yr, body mass index: 25-42 kg/m2) were randomly assigned to three groups for 12 wk of intervention; namely, a control group, a group on a 4.2 MJ/day diet, and a group on 4.2 MJ/day diet combined with aerobic and anaerobic exercise. Muscle morphology and biochemistry analysis were performed in 69 and 58 women, respectively. In contrast to the diet-only group, the die-plus- exercise group significantly increased the muscle fiber areas by 20-25%, the number of capillaries per muscle fiber type I by approximately 20%, and the activities of citrate synthase by approximately 35% and hexokinase by approximately 20% (P < 0.05). There were no statistically significant changes in any other muscle variable (P < 0.05). The respiratory exchange ratio decreased in both intervention groups by 2-4% (P < 0.01). It is concluded that 12-wk period of an energy-restrictive high-protein diet was not associated with major changes in muscle morphology or biochemistry. The addition of exercise to the die led to an adaptive increase in muscle fiber areas and in the oxidative capacity of the muscles.