Effectiveness of metformin on weight loss in non-diabetic individuals with obesity.

OBJECTIVE: The efficacy of metformin for the treatment of obesity has been evaluated in few clinical trials with inconclusive results. Moreover, the effectiveness in a real-life outpatient setting has not been tested until today. In this study we aimed to examine the effectiveness of metformin as a weight reducing drug in obese and overweight patients with regard to their degree of insulin resistance. DESIGN AND PATIENTS: We treated 154 consecutive patients with a body mass index ≥27 kg/m(2) in an outpatient setting over 6 months with metformin up to a dosage of 2,500 mg per day. Additionally, we included 45 untreated patients as controls. Patients were monitored for weight changes over 6 months. Before metformin treatment was started insulin sensitivity was determined in all patients by calculating HOMA index and Matsuda index after a 75 g oral glucose tolerance test. RESULTS: The mean weight loss in the metformin treated group was 5.8±7.0 kg (5.6±6.5%). Untreated controls gained 0.8±3.5 kg (0.8±3.7%) on average. Patients with severe insulin resistance lost significantly more weight as compared to insulin sensitive patients. The percentage of weight loss was independent of age, sex or BMI. CONCLUSION: Metformin is an effective drug to reduce weight in a naturalistic outpatient setting in insulin sensitive and insulin resistant overweight and obese patients.

Effect of long-term treatment with GH on bone metabolism, bone mineral density and bone elasticity in GH-deficient adults.

OBJECTIVE: Adults with GH deficiency (GHD) commonly have subnormal bone mineral density (BMD), and have been reported to have an increased risk of fractures. It has been suggested that GH replacement therapy may have beneficial effects on bone in such patients. The aim of this study was to investigate the effects of long-term GH replacement therapy on bone metabolism, BMD and bone elasticity in adults with GHD. DESIGN: At the start of the study, 20 adults with GHD were randomized to receive either GH, 0.25 IU/kg/week (the 'GH group') or placebo (the 'placebo group'). After 6 months, patients in the placebo group were switched to GH therapy, and all patients received GH for a further 42 months. PATIENTS: Of the 20 patients included in the study, 11 were male and nine were female. Mean age at the start of the study was 42.5 +/- 10.1 years. All patients had been GH-deficient for at least 2 years before the start of the study. MEASUREMENTS: Rates of bone resorption and formation were assessed by measuring serum levels of type I collagen carboxyterminal cross-linked telopeptide (ICTP) and carboxyterminal propeptide of type I procollagen (PICP), respectively. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the non-dominant forearm by single-photon absorptiometry (SPA). Bone elasticity was assessed by measuring apparent phalangeal ultrasound transmission velocity (APU). RESULTS: The main results in the GH group were as follows. The rate of bone resorption increased significantly during the first 6 months of treatment and remained significantly elevated above its baseline level thereafter. The rate of bone formation also rose during the first 6 months of treatment and remained elevated thereafter, but was significantly higher than at baseline only after 24 months of treatment. At both sites measured, BMD was subnormal at baseline, decreased during the first 6 months of treatment, and increased progressively for the rest of the study, eventually rising well above its baseline level. Bone elasticity decreased during the first 6 months of treatment, but had returned to its baseline level after 24 months. CONCLUSIONS: Our results support previous findings that BMD is subnormal in adults with GHD, that GH replacement therapy can stimulate bone turnover in such adults and that, in the long term, such stimulation results in a significant increase in BMD. In addition they show, for the first time, that BMD may continue to rise even after GH replacement therapy has been administered for 4 years, and indicate that bone elasticity is not adversely affected by long-term GH therapy.

Growth hormone substitution in growth hormone-deficient adults: effects on collagen type I synthesis and skin thickness.

Growth hormone stimulates collagen type I synthesis. Collagen type I is a common matrix compound in a large number of connective tissues. The aim of our study was to prove whether a stimulation of collagen type I synthesis might be accompanied by a deposition of collagen type I in the skin (cutis). Twenty growth hormone-deficient hypopituitary patients were included in a randomised, double-blind, placebo controlled, prospective, twelve-month study (eighteen patients assessable at the end of the study). The patients were treated with recombinant human growth hormone 0.25 U/kg/week subdivided in daily subcutaneous injections beginning with half the dosage during the first four weeks. During the first six months half of the patients were treated with placebo. PICP, the indicator of collagen type I synthesis, was increased after six months of therapy when compared to placebo. Skin thickness measured by ultrasound at the forearm and mechanically at the dorsum of the hand with strong compression of the skin both increased significantly following growth hormone substitution. Our data indicate that the stimulation of collagen type I synthesis by growth hormone substitution is followed by a deposition of collagen type I in the skin.

Peripheral osteopenia in adult patients with insulin-dependent diabetes mellitus.

Alterations in bone metabolism in diabetes mellitus is a topic of special interest. Bone blood flow is increased in the distal limb of diabetic patients, which is believed to increase osteoclastic activity. We measure bone mineral density using dual-photon absorptiometry in the distal lower limb, the femoral neck, and the lumbar spine in 41 IDDM patients and in 30 control persons. In the diabetic group there was a 10% reduction of bone mineral density in the femoral neck (p < 0.01) and a 12% reduction in the distal limb (p < 0.001) compared with the control group. No significant difference was found in the lumbar spine (p = 0.22). Our data yield incidence for peripheral osteopenia in IDDM-patients, independent of any systemic bone disease such as osteoporosis. A link between decreased bone mineral density and diabetic neuropathy has been observed for the femoral neck (p < 0.001), but not for the distal limb or axial skeleton. Whether there is a common aetiological link or a casual connection between diabetic neuropathy and bone mineral density has still to be determined.

Validation of a mechanical method for measuring skin thickness: relation to age, body mass index, skin thickness determined by ultrasound, and bone mineral density.

In a number of endocrine disorders, typical changes in skin thickness can be observed which make measurement of skin thickness interesting in this field. A newly developed mechanical method for measuring skin thickness is presented. Using a digital measuring screw on the dorsum of the hand with a defined measuring force of 10 newton and a resulting tissue compression of 1500 mm Hg, highly reproducible results were obtained (mean coefficient of variation 2.56%). In 129 women, 37 to 78 years old, body mass index < 30 kg/m2, there was no significant relation between body mass index and skin fold thickness. A negative correlation between skin fold thickness and age (r = 0.37, p < 0.001) was detected. This has been shown for skin by other methods previously and is well known to occur in bone, another tissue whose matrix as well as dermis consists mainly of collagen type I. In 30 subjects, half hypopituitary patients, half healthy subjects (17 women, 13 men; 43.3 +/- 10.5 years old), skin fold thickness measured mechanically and sonographically determined skin thickness correlated with r = 0.46 (p < 0.01). A significant correlation between bone mineral density measured by single photon-absorptiometry at the ultradistal forearm and skin fold thickness measured mechanically was found and skin fold thickness measured mechanically was found (r = 0.36, p < 0.05), whereas this was not the case for sonographically determined skin thickness and bone mineral density (r = 0.13, n.s.). This newly developed method might be useful in clinical studies on endocrine disorders affecting skin (and bone) metabolism and the regulation of collagen type I metabolism in general.

[Backache and osteoporosis in perimenopausal women]. / Rückenschmerzen und Osteoporose bei perimenopausalen Frauen.

Osteoporosis is thought to represent one of the main causes of back pain in perimenopausal women. One hundred perimenopausal women (45 to 60 years) who were consecutively admitted in order to clarify the cause of their back pain were examined. In 20% disc degenerations were found. Other degenerative disorders (osteoarthritis) of the spine without coincident scoliosis were found to be the second most common cause of pain in 19%. Scoliosis due to different leg length was detected in 15%, idiopathic scoliosis in 13%. Spondylolisthesis occurred in 7% even more frequently than osteoporosis with vertebral deformities in 6%. Non-osteoporotic vertebral deformities were seen as often as osteoporotic ones. Rare diagnoses among others were seronegative spondyloarthropathy and fibrositis. Our results indicate that back pain in women up to 60 years is mostly due to degenerative disorders of the spine. Osteoporosis with vertebral deformities as cause of pain is quite rare. Comparing bone mineral density of the distal forearm (SPA) of the patients with back pain not due to manifest osteoporosis (98 +/- 15% of age related mean) with those of 50 asymptomatic women (96 +/- 14%) and 50 female patients with pain in other regions of the skeleton (103 +/- 17%) in the same age group, there was no evidence for any relation between low bone mineral density and skeletal pain.