[Primary hyperparathyreoidism - diagnostic procedures and management]. / Primärer Hyperparathyreoidismus ­ Diagnostik und Therapie.

Hypercalcemia as a laboratory result is often diagnosed during evaluation for osteoporosis. Any form of hypercalcemia should be evaluated further. Owing to fluctuating calcium levels, the measurement should be repeated and corrected for elevated albumin levels by calculation or by measuring ionized calcium. In the diagnosis of primary hyperparathyroidism, measurement of parathyroid hormone, creatinine/glomerular filtration rate, phosphate, 25-OH vitamin D3 and 24-hour urine values are essential for differential diagnosis. Kidney ultrasound is used to detect nephrocalcinosis or kidney stones, and dual-energy X-ray absorptiometry (DXA) to determine bone mineral density (BMD) at the lumbar spine, femoral neck, total femur, and distal forearm. Complete cure is only possible through surgical resection of the adenoma(s). The indication for surgery is dependent on the age of the patient, existing complications, and the patient's preference. Diagnostic imaging should only be performed if surgery is planned. Typically, neck ultrasound and 99mTc MIBI scintigraphy are sufficient to localize the parathyroid adenoma. Presurgical diagnostic evaluation of the thyroid is reasonable for surgical planning. Vitamin-D deficiency should be normalized before surgery. Postsurgical calcium and vitamin-D administration will prevent postsurgical hypocalcemia and hungry-bone disease, and may optimize the outcome of BMD. Treatment of osteoporosis without fractures might not be necessary, owing to normalization of BMD several years after parathyroid surgery. The continuation of specific anti-osteoporotic treatment with bisphosphonates post-surgery did not have any advantage and hence cannot be recommended.

Risk factors for decline in renal function among young adults with type 1 diabetes.

AIMS: To investigate risk factors for declining renal function among subjects with type-1-diabetes. METHODS: Observational study based on data from the diabetes registry DPV. 4424 type-1-diabetes subjects aged ≥18 years, age at onset <18 years were identified. Modification of Diet in Renal Disease (MDRD) equation was used to estimate glomerular filtration rate (eGFR). Annual rate of renal decline was estimated for each patient using hierarchic linear regression models. Additional regression models were fitted to adjust for covariates. RESULTS: Median age was 26 [Q1; Q3: 21; 39] years. Annual decline of renal function was -1.22 (95% CI: -1.50; -0.94) ml/min/1.73 m2. At baseline, higher eGFR was related to more rapid decline compared to impaired or reduced eGFR (GFR ≥ 90: -2.06 (-2.35; -1.76), 60 ≤ GFR < 90: 0.45 (0.08; 0.81), GFR < 60: 0.52 (-0.24; 1.29) ml/min/1.73 m2, p < 0.01). During follow-up, the highest decline was associated with reduced renal function, whereas the lowest decline was related to normal kidney function (p < 0.01). Poor metabolic control (p = 0.04), hypertension (p < 0.01) and albuminuria (p = 0.03) were associated with more rapid loss of kidney function. No difference was observed among insulin regimen. CONCLUSION: Among this large type-1-diabetes cohort, more rapid loss of kidney function was related to higher baseline eGFR, log-term worse metabolic control and diabetic comorbidities.

Exercise training-induced adaptations associated with increases in skeletal muscle glycogen content.

Chronic exercise training results in numerous skeletal muscle adaptations, including increases in insulin sensitivity and glycogen content. To understand the mechanism leading to increased muscle glycogen, we studied the effects of exercise training on glycogen regulatory proteins in rat skeletal muscle. Female Sprague Dawley rats performed voluntary wheel running for 1, 4 or 7 weeks. After 7 weeks of training, insulin-stimulated glucose uptake was increased in epitrochlearis muscle. As compared with sedentary control rats, muscle glycogen did not change after 1 week of training, but increased significantly after 4 and 7 weeks. The increases in muscle glycogen were accompanied by elevated glycogen synthase activity and protein expression. To assess the regulation of glycogen synthase, we examined its major activator, protein phosphatase 1 (PP1), and its major deactivator, glycogen synthase kinase (GSK)-3. Consistent with glycogen synthase activity, PP1 activity was unchanged after 1 week of training but significantly increased after 4 and 7 weeks of training. Protein expression of R(GL)(G(M)), another regulatory PP1 subunit, significantly decreased after 4 and 7 weeks of training. Unlike PP1 activity, GSK-3 phosphorylation did not follow the pattern of glycogen synthase activity. The ~ 40% decrease in GSK-3α phosphorylation after 1 week of exercise training persisted until 7 weeks, and may function as a negative feedback mechanism in response to elevated glycogen. Our findings suggest that exercise training-induced increases in muscle glycogen content could be regulated by multiple mechanisms, including enhanced insulin sensitivity, glycogen synthase expression, allosteric activation of glycogen synthase, and PP1 activity.

Effects of exercise training on subcutaneous and visceral adipose tissue in normal- and high-fat diet-fed rats.

Regular physical activity improves glucose tolerance and decreases adiposity. Our aim was to investigate the effects of exercise training on subcutaneous (inguinal) and visceral (parametrial) adipose tissue in rats that were fed a chow diet (13% fat) or made insulin resistant by a high-fat diet (60% fat). Sprague-Dawley rats performed 4 wk of voluntary wheel running or were kept as sedentary controls. The training groups fed chow and the high-fat diet achieved similar running distances (8.8 +/- 1.8 and 9.3 +/- 1.9 km/day, respectively). Training improved oral glucose tolerance in chow-fed rats and prevented the glucose intolerance that occurred in sedentary rats fed the high-fat diet. In both subcutaneous and visceral adipose tissue, the high-fat diet-induced increases in fat pad weight (67% and 133%, respectively), adipocyte size (20% and 43%), and cell number (36% and 65%) were completely prevented by exercise training. Cytokine mRNA expression in visceral fat did not change with exercise training. However, in subcutaneous fat, training actually increased mRNA expression of several cytokines [IL-6: 80% (P < 0.05); TNF-alpha: 100% (P < 0.05); IL-1 receptor antagonist (IL-1Ra): 57% (P = 0.08)] with no detectable increases in serum cytokine concentrations. In summary, exercise training can overcome high-fat diet-induced impairments in glucose tolerance and increases in adipocyte size, cell number, and fat pad mass. Improved glucose tolerance was accompanied by an increase in cytokine gene expression in subcutaneous fat. This finding raises the possibility of a specific role of subcutaneous adipose tissue in adaptive responses to exercise training.