Search

Udgivelsesdato: 2008

OBJECTIVE: To assess the effect of substitution of early insulin release with a small weight-based dose of the rapid acting insulin analogue, insulin Aspart (IAsp), on postprandial hyperglycaemia in patients with recently diagnosed type 2 diabetes. MATERIAL AND METHODS: In a randomized, double-blind, double-dummy design, 20 patients underwent three 3-day periods with injection of IAsp 0.06 IU/kg BW or placebo 30 min before main meals. The effect on blood glucose fluctuations was evaluated using a continuous glucose monitoring system. Efficacy endpoints were time with glucose values above 8 mmol/L and glucose area above 8 mmol/L; safety endpoint was time with glucose values below 4 mmol/L in the last 24 h in the treatment periods. RESULTS: IAsp significantly reduced the duration of blood glucose values above 8 mmol/L compared with placebo during 24 h (8.1+/-1.4 h versus 12.7+/-1.3 h), (p<0.03). Glucose areas above 8 mmol/L were 0.6+/-0.2 mmol/lxh and 1.2+/-0.2 mmol/lxh for IAsp and placebo, respectively (p<0.001). Two patients (one in each of the IAsp and placebo periods) had two asymptomatic episodes of glucose registration below 4 mmol/L. Patients with HbA(1c) below 7.4 % obtained the greatest reduction in duration of blood glucose values above 8 mmol/L, whereas the decrease in blood glucose increments for patients with HbA(1c) above 7.4 % was not significantly different from placebo. CONCLUSIONS: A fixed dose of IAsp injected 30 min before mealtimes reduced the postprandial glucose increment in patients with recently diagnosed type 2 diabetes without the risk of hypoglycaemia. Glucose fluctuations in patients with HbA(1c) below 7.4 % improved to near normal level Udgivelsesdato: 2008

OBJECTIVE: It has been hypothesized that increased free insulin-like growth factor (IGF)-I levels generated from an increase in IGF-binding protein (IGFBP) protease activity could be the inhibitory mechanism for the decreased growth hormone (GH) secretion observed in obese subjects. RESEARCH METHODS AND PROCEDURES: In this study, we determined basal and 24-hour levels of free IGF-I and -II, total IGF-I and -II, IGFBP-1, as well as basal IGFBP-2, -3, and -4, acid-labile subunit (ALS), IGFBP-1, -2, and -3 protease activity, and 24-hour GH release in obese women before and after a diet-induced weight loss. Sixteen obese women (age, 29.5+/-1.4 years) participated in a weight loss program and 16 age-matched non-obese women served as controls. RESULTS: Circulating free IGF-I and 24-hour GH release were significantly decreased in obese women at before weight loss compared with non-obese women (1.29+/-0.12 vs. 0.60+/-0.09 microg/L; p<0.001 and 862+/-90 vs. 404+/-77 mU/24 hours; p<0.001, respectively). Free IGF-I and 24-hour GH release were not inversely correlated to each other. IGFBP-1 and -2 levels were decreased, whereas ALS, IGFBP-3 and -4, and IGFBP-1, -2, and -3 protease activity were similar in obese and non-obese women. Eight of the 16 obese women achieved an average weight loss of 30+/-5 kg during 26 to 60 weeks of dieting. After the considerable weight loss, significant differences in free IGF-I, GH release, and IGFBP-1 and -2 levels were no longer present between previously obese and non-obese women. DISCUSSION: We showed that circulating free IGF-I is markedly decreased in severely obese women and does not per se mediate the concomitant hyposomatotropism. The decreased levels of free IGF-I seem to be transient and restored to normal levels after weight loss. Udgivelsesdato: 2007-Apr

AIMS: To describe body composition in patients with Type 1 diabetes at diagnosis and during the first year after initiation of insulin therapy. RESEARCH DESIGN AND METHODS: In 10 (eight male and two female) newly onset Type 1 patients, age 31.5 +/- 3.2 years (27-37 years) (sd and range), body mass index (BMI) 20.8 +/- 1.6 (19.2-23.4) kg/m2, body composition was estimated by means of dual-energy X-ray absorptiometry (DXA) whole body scanning supplemented by estimation of total body water (TBW) (isotope dilution technique with 3H2O) at diagnosis and after 1, 3, 6 and 12 months of insulin therapy. RESULTS: During the first year after onset of diabetes body weight (BW) increased 4.3 +/- 2.9 (0.1-8.3) kg (P = 0.0012) distributed as a 13.3% (1.6 kg) increase in total fat mass (FM) and 4.9% (2.5 kg) increase in lean body soft tissue mass (LBM). The self-reported weight loss at onset was 6.3 +/- 2.5 kg (1.5-10.0 kg). Compared with two reference populations the Metropolitan Life Insurance Co. and a healthy age and sex-matched local DXA scanned group the initial body composition data demonstrated BW 6.2 kg below ideal weight and a significant reduction of the FM (25% or -0.87 sd), whereas LBM was within the expected range. CONCLUSIONS: During the first year after onset of Type 1 diabetes the mean increase in BW is 6.5% with a 13.3% increase in FM and a 4.9% increase in LBM. Self-reported data on premorbid BW suggest an approximately 10% reduction in BW at onset of Type 1 diabetes. Compared with a healthy reference population initial body composition data demonstrate a 25% reduction of the FM, whereas only a minor and non-significant reduction in the LBM is encountered. These data indicate that uncontrolled diabetes is rather a fat catabolic state than, as previously believed, a protein catabolic state.

The purpose of the present study was to evaluate the combined effect of GH treatment on body composition and glucose metabolism, with special focus on beta-cell function in adult GHD patients. In a double-blind placebo-controlled design, 24 GHD adults (18M/6F), were randomized to 4 months treatment with biosynthetic GH 2 IU/m2s.c. daily (n =13) or placebo (n =11). At inclusion and 4 months later an oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT) and dual-energy X-ray absorptiometry (DXA) whole-body scanning were performed. During the study period, body weight decreased 1.6 kg from 94.0 +/- 18.7 to 92.4 +/- 19.4 kg (mean +/- SD) (P<0.05) in the GH-treated group, but remained unchanged in the placebo group. Fat mass decreased from 32.4 +/- 9.6 to 28.1 +/- 10.5 kg (P<0.001), whereas lean body mass increased from 58.3 +/- 11.5 to 61.0 +/- 11.7 kg (P<0.01) in the GH-treated group. Treatment with GH for 4 months resulted in a significant increase in fasting blood glucose (before GH 5.0 +/- 0.3 and after 5.4 +/- 0.6 mmol/l, P<0.05), fasting plasma insulin (before GH 38.4 +/- 30.2 and after 55.3 +/- 34.7 pmol/l, P<0.02) and fasting proinsulin (before 8. 1 +/- 6.7 and after 14.6 +/- 16.1 pmol/l, P<0.05). The insulin sensitivity index SI, estimated by Bergmans Minimal Model, decreased significantly [before GH 1.1 +/- 0.7 and after 0.4 +/- 0.2 10(-4)(min x pmol/l), P<0.003]. The non-insulin-dependent glucose uptake (glucose effectiveness SG did not change (before GH 0.017 +/- 0.005 and after 0.015 +/- 0.006 min-1, NS). Insulin secretion was enhanced during GH therapy, but insufficiently to match the changes in SI, resulting in a higher blood glucose level during an OGTT. Blood glucose at 120 min was 5.5 and 6.3 mmol/l before and after GH treatment, respectively (P = 0.07). One patient developed impaired glucose tolerance. Short-term GH replacement therapy in a dose of about 2 IU/m2 daily in GHD adults ind

A total of 16 obese women (body mass index (BMI) 30-43 kg m(-2)) participated in a weight reduction study. Before and after a weight loss of 11.7 +/- 7.4 kg (mean +/- SD), body composition was assessed by dual energy X-ray absorptiometry (DXA), and total body potassium counting (TBK). These measurements were compared with bioimpedance analysis (BIA) by applying 11 predictive BIA equations published in the literature. Predictive equations for the present study population were developed, with the use of fat-free mass (FFM) as assessed by TBK and DXA as references in multiple regression analysis. The results of the BIA equations varied widely; FFM was generally overestimated by BIA as compared with DXA and TBK before and after weight loss. During weight loss, the FFM did not change, as estimated by DXA (1.3 +/- 2.3 kg, p > 0.05) and TBK (0.9 +/- 2.9 kg, p > 0.05). The recorded change in impedance (R) was also insignificant. Three BIA equations from the literature, which were not specific for the degree of obesity in the present study group, predicted changes in FFM (from 0.5 + 3.6 to 2.4 +/- 4.4kg, p > 0.05) that were comparable with those estimated by the reference methods. Eight equations from the literature, which included equations specific for the degree of obesity in the study group, and the group specific equations developed for the present population predicted significant changes in FFM during weight loss (from 2.3 +/- 3.0 to 5.0 +/- 3.0 kg, p < 0.05). We conclude that in obesity most predictive equations are unable to predict static body composition and are not reproducible for individuals over time. However, a significant or insignificant change in R (without accompanying predictive equations) may be used to indicate whether FFM is lost or preserved in groups of obese subjects.

OBJECTIVE: To validate the ability of DXA to measure total body composition before and after weight loss and the composition of the lost body mass.DESIGN: Cross sectional and follow-up study of body composition before and after a weight loss of 10.6 +/- 6.8 kg.SUBJECTS: 31 obese subjects with a mean body weight of 105.2 +/- 15.2 kg at baseline, and a mean body weight of 94.6 +/- 16.5 kg at follow-up.MEASUREMENTS: Body composition was measured by dual X-ray absorptiometry, total body potassium counting, and high precision scales before and after a weight loss.RESULTS: DXA and the scales showed a strong linear relation (r = 1). At baseline, however, DXA underestimated the body weight by a maximum of 3.2 kg because the subjects were too large for the scan table. After weight loss body weight measurements were accurate. Before and after weight loss the linear relations between DXA and TBK for FFM were strong (r = 0.92 and 0.93). Bland and Altman plots showed limits of agreement of +/-9 kg before and after weight loss; DXA underestimated FFM in women and overestimated FFM in men. DXA accounted for 80% of the lost body weight. The composition of the lost body mass did not differ from that estimated by TBK (7.6% FFM and 92.4% FM by TBK; 11% FFM and 89% FM by DXA).CONCLUSION: DXA estimates accurately the body composition and the composition of weight loss in groups of obese subjects. However, the scan table may be too small for patients weighing more than 95 kg.

OBJECTIVE: To investigate the impact of obesity, fat distribution and weight loss on collagen turnover using serum concentrations of the carboxyterminal propeptide of type I procollagen (S-PICP) and the aminoterminal propeptide of type III pro-collagen (S-PIIINP) as markers for collagen turnover.DESIGN: Blood samples were obtained once at baseline, and after 8 and 16 weeks of dietary treatment (5.0 MJ/day diet).SETTING: Outpatient clinic of Hvidovre University Hospital.MAIN OUTCOME MEASURES: S-PICP, S-PIIINP, fat distribution and weight loss.RESULTS: S-PIIINP was associated with body weight (r = 0.37; P = 0.004), height (r = 0.27; P = 0.04), waist circumference (r = 0.35; P = 0.007), as well as with WHR (r = 0.33; P = 0.01) and was inversely correlated to age (r = -0.40; P = 0.002). Compared with randomly selected controls from a large pool of healthy volunteers, the obese patients had elevated S-PIIINP values before as well as during weight loss, whereas S-PICP levels were within the normal range and did not correlate with any anthropometric measures. The average weight loss after 16 weeks dietary treatment was 8.1 kg (s.d. = 0.8). S-PIIINP decreased during the 16 weeks of energy restriction (P < 0.05) and changes in S-PIIINP was correlated to body weight loss (r = 0.32; P < 0.05) and to changes in waist circumference (r = 0.34; P < 0.05) as well as changes in WHR (r = 0.30; P < 0.05).CONCLUSION: S-PIIINP is elevated in obesity and associated with body fat distribution, suggesting an increased turnover of type III collagen related to obesity in general and to abdominal obesity in particular. S-PIIINP levels decreases during weight loss in obese subjects, whereas S-PICP levels seems un-related to obesity and weight loss.

Data on body composition in patients with insulin-dependent diabetes mellitus (IDDM) are scarce. Dual X-ray absorptiometry (DXA) scanning has proved useful for this purpose in other groups of patients. We tested the validity of the DXA scanner for the determination of fat-free mass (FFM) and fat mass in IDDM patients and control subjects, as compared to other reference methods, i.e. total body potassium by 40K whole body counting (TBK), total body water by tritiated water (TBW), bioelectrical impedance analysis (BIA) and 24-h urinary creatinine excretion (Ucrea). A total of 13 healthy controls, 5 males and 8 females, aged 34.2 years +/- SD 10.4, and 11 IDDM patients, 5 males, 6 females, aged 28.1 years +/- 7.3, diabetes duration 4.2 +/- 2.9 (1.0-9.9), were examined. The patients had no long-term diabetic complications and they had normal ophthalmoscopy and urine albumin excretion. The agreement between FFM estimated by DXA and the other methods, expressed as mean difference +/- 2 SD was; for DXA vs. TBK, 0.09 +/- 6.26 and 0.50 +/- 5.26 kg for controls and IDDM patients respectively; DXA vs. TBW, -2.07 +/- 2.56 and -1.07 +/- 4.58 kg; DXA vs. Ucrea, -2.62 +/- 8.02 and 2.00 +/- 10.0 kg; DXA vs. BIA, -7.90 +/- 8.92 and -7.85 +/- 2.32 kg. The results obtained with BIA were significantly different from the other methods for both control subjects and IDDM patients. In conclusion, DXA scanning is a precise and valid method for estimation of fat-free mass in IDDM patients.

In the present study, we 1) determined whether the impaired spontaneous 24-h GH secretion as well as the blunted GH response to provocative testing in obese subjects are persistent disorders or transient defects reversed with weight loss and 2) investigated 24-h urinary GH excretion and basal levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), as well as insulin in obese subjects before and after a massive weight loss. We studied 18 obese subjects (age, 26 +/- 1 yr; body mass index, 40.9 +/- 1.1 kg/m2); 18 normal age-, and sex-matched control subjects; and 9 reduced weight obese subjects after a diet-induced average weight loss of 30.3 +/- 4.6 kg. Twenty-four-hour spontaneous GH secretion was estimated by obtaining 3240 integrated 20-min blood samples using a constant blood withdrawal technique and computerized algorithms. Body composition was determined using anthropometric measurements and dual energy x-ray absorptiometry scanning (DXA). In the obese subjects, 24-h spontaneous GH release profiles and the GH responses to insulin-induced hypoglycemia and L-arginine as well as basal IGF-I levels and the IGF-I/IGFBP-3 molar ratio were decreased, whereas insulin levels were elevated compared to those in normal subjects. In obese subjects, 24-h spontaneous GH secretion and serum IGF-I levels were inversely related to abdominal fat (r = -0.67; P <0.01) and percent body fat (r = -0.69; P <0.01), respectively. The decreased 24-h spontaneous GH release profiles, the decreased GH responses to insulin-induced hypoglycemia and L-arginine, the decreased basal IGF-I levels and IGF-I/IGFBP-3 molar ratio, as well as the elevated insulin levels were returned to normal after a massive weight loss in the obese subjects. In conclusion, the present study has shown reversible defects in 24-h spontaneous GH release profiles, basal IGF-I levels, and the IGF-I/IGFBP-3 molar ratio in obese subjects. The recovery of the 24-h GH release points to an acquired