Genotype-phenotype correlations and response to glucose lowering therapy in subjects with HNF1ß associated diabetes.

AIMS: Molecular defects of hepatic nuclear factor 1ß (HNF1ß) are associated with multiorgan disease (renal disease, pancreatic hypoplasia, and genital tract anomalies) in addition to diabetes. We examined the phenotypic features, insulin secretory response to glucose, and response to treatment in subjects with HNF1ß-MODY (MODY 5). METHODS: Twelve subjects with HNF1ß-MODY were phenotyped in detail. A 2-h oral glucose tolerance test was performed to establish insulin secretory response with glucose, insulin and C-peptide measurements taken at baseline and 30 min intervals. Clinical follow-up occurred bi-annually. RESULTS: Ten of 12 subjects had diabetes with mean age of onset of 30.2 ± 15.5 years, fasting glucose of 9.7 ± 4.6 mmol/L and HbA1c of 60.9 ± 17.1 mmol/mol (7.7 ± 1.6%). Renal and/or pancreatic morphological abnormalities were found in 9 subjects. Mean fasting C-peptide (0.5 ± 0.4 nmol/L) and AUC C-peptide (1.5 ± 1.0 nmol/L/120 min) were reduced in our cohort with 4 subjects demonstrating marked insulin deficiency. OGIS was reduced at 290.2 ± 67.0 ml min-1 m-2. 6/10 subjects were on insulin therapy at initial diagnosis and 8/10 at last clinical follow-up. Mean insulin dose at last clinical follow-up was 0.45 ± 0.23units/kg/day. 5 subjects on insulin were trialled on sulphonylurea therapy, and none was successfully weaned off insulin. CONCLUSIONS: Diagnosing HNF1ß-MODY in a diabetes clinic is challenging due to its variable phenotype and variable age of onset. ß-Cell dysfunction and insulin resistance contribute to diabetes in HNF1ß-MODY. No subjects successfully transitioned to sulphonylurea. Early initiation of insulin therapy would be suitable to achieve glycaemic control. This emphasizes the importance of genetic testing for monogenic forms of diabetes to guide personalized treatment.

Statistical analysis of fat and muscle mass in osteoporosis in elderly population using total body DXA scans.

BACKGROUND: The magnitude of effects of lean mass and fat mass on bone health is controversial, and this study is a contribution to understand its effects on skeletal composition. AIM: We explored the relationship of body fat and muscle parameters with bone mineral density (BMD) and age and observed if it changed when matched with body mass index (BMI) of the same study subjects. METHODS: One-hundred sixty-four community dwelling, ambulatory elderly attending the osteoporosis services of a Dublin hospital was recruited. Out of these, 158 female patients had a total body DXA scan, and their body composition outcomes were included in this analysis. The relationship between body fat and muscle composition and BMD at all sites was determined and also matched by BMI. RESULTS: Total-Body BMD had a strong positive correlation with lean mass(r = 0.492, p 0.00) and fat mass(r = 0.414, p 0.00), though lean mass remained the strongest predictor of BMD at all sites. Increasing BMI categorically had a positive effect on both lean mass and fat mass. Increasing age was significantly associated with an increase in fat mass(r = 2.40, p 0.00) and a decrease in muscle mass(r = 0.478, p 0.01). CONCLUSION: Both lean mass and fat mass are significant predictors of BMD. To preserve BMD maintenance or increase of lean mass is more effective than fat mass. BMI correlates well with body composition; however, we recommend the use of direct measures of body fat and muscle to make this relation more interpretable. Total Body DXA is a readily available diagnostic tool which provides high-valued information about body composition.

Treatment of osteoporosis with recombinant parathyroid hormone, utilisation of total body DXA to observe treatment effects on total body composition and factors determining response to therapy.

PURPOSE: Recombinant parathyroid hormone (rPTH) increases bone mineral density (BMD). However, certain other potential effects of rPTH remain to be studied. The aim of this study is to identify whether bone turnover markers, relevant biochemical parameters or total body fat and muscle composition affect the response to rPTH and to establish if these parameters in particular change during treatment. METHODS: One hundred seventy-two participants were treated with rPTH, and 128 subjects who fully complied with the therapy and completed their investigations including biochemical bone markers and total body composition at baseline, 6 months and 1 year of the treatment were divided into responder and non-responder groups. A total body dual-energy X-ray absorptiometry (DXA) scanner was used to assess the body muscle, fat and bone composition. RESULTS: rPTH significantly increased BMD spine at 1 year (p = 0.000). Twenty-four-hour urinary calcium was significantly increased at 6 months in the responder group (p = 0.00). There was a trend to an increase in the fat and muscle mass (p = 0.52 and 0.45, respectively), and it was not negatively affected by rPTH. Bone turnover markers (P1NP and OC) did not show statistically significant difference over time between responders and non-responders (p = 0.74 and p = 0.19, respectively). CONCLUSIONS: Hypercalciuria which is a frequent feature in osteoporotic population may predict non-responders at 6 months of rPTH, and it may help to optimise individual patient's treatment. Unlike endogenous PTH in pathological conditions, rPTH is anabolic to bone and has no detrimental effects on the body fat and muscle composition.

Malnutrition in the elderly and its effects on bone health - A review.

This article aims to provide an overview of the prevalence, causes and risk factors associated with malnutrition in the elderly. It includes the clinical consequences and economic impact of malnutrition in the elderly and in particular the osteoporotic population. It encompasses the significance of dietary protein and its effects on bone health.