Aim: To analyze whether bone mineral density (BMD) and bone resorption status are influenced by long-term metabolic control and duration of disease in adolescents with long-standing type 1 diabetes mellitus. Methods: Twenty-seven adolescents (age 13.1 ± 1.7 years, duration of diabetes 6.9 ± 3.0 years) were studied. The BMD, expressed as z score, was measured at the lumbar spine (L1–L4) using dual-energy X-ray absorptiometry, while the urinary excretion of total deoxypiridinoline (Dpyd), a marker of bone resorption, was measured by immunoassay and was corrected by creatinine (Cr). Linear and multivariate correlations between lumbar BMD z score or Dpyd/Cr excretion and age and disease variables [short-term (Hb A_1clatest) or long-term (Hb A_{1cwholeduration}) metabolic control, duration, ‘diabetes impact index’ (mean Hb A_{1cwholeduration} x duration of disease in months)] were sought. Results: In diabetic subjects the mean BMD z score was –0.44 ± (SD) 1.02 (95% CI: –0.03; –0.84), and the Dpyd/Cr excretion was not increased. A negative correlation was found between lumbar BMD z score and age (r –0.59; p = 0.001), duration (r –0.39; p = 0.04), and the diabetes impact index (r –0.4; p = 0.04). The Dpyd/Cr ratio correlated negatively with age (r –0.40; p = 0.04) and positively with height velocity (r 0.42; p = 0.04). By using multiple linear regression, age showed a significant inverse correlation with lumbar BMD z score (β = –0.39; p = 0.0005). A negative correlation was found between lumbar BMD z score and Hb A_{1cwholeduration} (β = –0.40; p = 0.02) or diabetes impact index (β = –0.001; p = 0.01). Conclusions: Poor metabolic control may expose adolescents with long-standing type 1 diabetes to the risk of developing osteopenia in adult age. Optimization of metabolic control in growing diabetic children may prevent osteoporosis in later life.

Insulin-stimulated glycogen synthase activity in human skeletal muscle correlates with insulin-mediated glucose disposal rate (M) and is reduced in insulin-resistant subjects. We have previously reported reduced insulin-stimulated glycogen synthase activity associated with reduced fasting glycogen synthase phosphatase activity in skeletal muscle of insulin-resistant Pima Indians. In this study we investigated the time course for insulin stimulation of glycogen synthase and synthase phosphatase during a 2-h high-dose insulin infusion (600 mU/min per m2) in six insulin-sensitive Caucasians (group S) and in five insulin-resistant Pima Indians (group R). Percutaneous muscle biopsies were obtained from the quadriceps femoris muscle after insulin infusion for 0, 10, 20, 40, and 120 min.In group S, insulin-stimulated glycogen synthase activity increased with time and was significantly higher than in group R. In group S. synthase phosphatase activity increased significantly by 25% at 10 min and then decreased gradually. No significant change in synthase phosphatase was seen in group R and activity was lower than group S at 0 to 20 min.These data suggest that a low basal synthase phosphatase activity and a defect in its response to insulin explain, at least in part, reduced insulin stimulation of skeletal muscle glycogen synthase associated with insulin resistance. (J. Clin. Invest. 1990. 85:476-481.) insulin -glycogen synthase -protein phosphatase * muscle

OBJECTIVE: To detect predictive variables of weight changes in non-obese women. DESIGN: Three year follow-up study. SUBJECTS: Fifty-eight women (age 40.0 AE 12.8 y, height 159 AE 7 cm, weight 62.5 AE 9.6 kg and body mass index ((BMI) 24.7 AE 3.7 kgam 2 ). MEASUREMENTS: At baseline, basal metabolic rate (BMR) and respiratory quotient (RQ) by indirect calorimetry. Weight and BMI at baseline and after 3 y. RESULTS: In both univariate and multivariate analyses, age and RQ at baseline were signi®cant predictors (P`0.05) of subsequent changes in weight and BMI. CONCLUSION: In non-obese women, RQ and age are independent predictors of subsequent weight changes.

Objective: Glucocorticoid excess is widely recognized as one of the most important causes of bone loss. The mechanism of glucocorticoid-induced osteoporosis is presumably multifactorial, and consists of the loss of organic and non-organic compounds. Efforts have been made to develop simple physical methods for the assessment of bone tissue for the screening of subjects at high risk of osteoporosis, without the use of radioactive sources or ionizing radiation. Quantitative ultrasonometry (QUS) has been suggested as a useful method for monitoring patients undergoing glucocorticoid therapy, which is the most common cause of glucocorticoid excess. QUS appears to detect more structural bone changes than the traditional methods and allows assessment of bone density and elasticity, both characteristics influenced by organic and non-organic bone compounds. However, the use of QUS has not yet been extensively investigated in subjects with endogenous cortisol excess. The aim of this study was to evaluate the usefulness and predictive power of QUS in assessing bone loss in subjects with differing degrees of endogenous cortisol excess due to adrenal mass. Design: Thirty-four patients (20 women and 14 men) aged between 21 and 59 years were evaluated; fifteen (9 women and 6 men; median age, 42 years) were affected by overt Cushing's syndrome (CS) and nineteen (11 women and 8 men; median age, 44 years) by subclinical CS, defined as lacking clinical signs of hormone excess despite the presence of at least two abnormalities in hypothalamic± pituitary±adrenal axis function, as assessed by routine endocrine tests. All women included were eumenorrhoic. Methods: QUS measurement of amplitude-dependent speed of sound was performed on the 2nd to 5th proximal phalanges of the non-dominant hand using a DBM Sonic 1200R bone profiler (Igea S.r.l, Italy). The results were compared with bone density assessed on lumbar vertebrae (L1±L4) and femoral neck sites by dual-energy X-ray absorptiometry (DEXA). Results: A strongly significant bone loss was detected by finger QUS measurement when the patients were considered either all together or as two subgroups P , 0X001, all). The bone density decrease in the fingers was similar to that found at the lumbar spine and femoral neck by the DEXA technique. Lumbar and finger Z-scores correlated inversely with 24 h urinary free cortisol (UFF) excretion P , 0X01, both). Finger Z-scores also correlated inversely with the estimated duration of subclinical CS P , 0X05X Concerning disease activity, only UFF was confirmed by multivariate analysis to be an independent factor influencing bone loss P , 0X05X A positive correlation between the results of the two techniques was found in controls P , 0X05 but not in patients. The lack of correlation between the two techniques in patients can probably be attributed to the different parameters of bone alteration measured by the techniques. Conclusions: The detection of bone loss in subclinical CS similar to that in overt CS suggests that all subjects with endog...

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