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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Diabetes mellitus ; bone ; COL1A1 polymorphism ; vitamin D ; parathyroid hormone ; bone markers.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Osteopenia is a recognised complication of diabetes mellitus which could be due to abnormal bone turnover or disturbances in the calcium/parathyroid hormone/vitamin D axis or both. Genetic factors also play an important part in determining bone mass although this has not been studied in diabetes. Recently a polymorphism of the collagen type 1 α 1 (COL1A1) gene has been shown to be associated with low bone mass in British women. To identify subjects with diabetes who may be at risk of developing osteoporosis and fractures, we analysed bone mineral density in relation to the biochemical markers of bone turnover, calcium homeostasis and the COL1A1 genotype in a group of premenopausal women with Type I (insulin-dependent) diabetes mellitus (n = 31), Type II (non-insulin dependent) diabetes mellitus (n = 21) and control subjects (n = 20). Bone mineral density was lower at the femoral neck in the subjects with Type I diabetes (p = 0.08) as were serum 25-hydroxyvitamin D compared with control subjects (p = 0.023) and this was negatively correlated with serum collagen type 1 C-terminal propeptide (r = –0.56, p 〈 0.001). Bone mineral density in Type II diabetes was not different from control subjects, after correction for body mass index. Bone resorption was, however, raised in the Type II diabetic subjects as reflected by the higher urinary deoxypyridinoline values (p = 0.016) and lower collagen type 1 C-terminal propeptide:deoxypyridinoline ratio (p = 0.04). In the whole group studied, subjects with the COL1A1 ’s' genotype had lower bone mineral density at the femoral neck (p = 0.01) which was partly attributable to a lower body mass index. Following multiple regression analysis body mass index and collagen type 1 C-terminal propeptide concentrations remained determinants of bone mass at all three sites, whereas genotype appeared to be a predictor of bone mass at the femoral neck only. We conclude that measurement of these variables could prove useful in firstly identifying those diabetic women at risk of osteoporosis and secondly guiding therapeutic intervention. [Diabetologia (1998) 41: 1314–1320]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; renal haemodynamics ; improved glycaemic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The impact of improved glycaemic control on renal function in newly-presenting Type 2 (non-insulin-dependent) diabetic patients has not been adequately researched. Consequently, glomerular filtration rate and effective renal plasma flow and urinary albumin excretion rates were determined in 76 subjects (age (mean (SD)): 54 (9.5) years; 50 male) of an original cohort of 110 newly-presenting normotensive non-proteinuric Type 2 diabetic patients following 6 months treatment with diet alone (n=42) or with oral hypoglycaemic agents (n=34). Significant reductions were observed in (presentation vs 6 months): body mass index (p〈0.01); fasting plasma glucose (p〈0.001); glycated haemoglobin (HbA1) (p〈0.001); systolic blood pressure (p〈0.01); and diastolic blood pressure (p〈0.001). Glomerular filtration rate declined from 117 (22) to 112 (21) ml·min−1 (p〈0.01), with unchanged effective renal plasma flow (534 (123) vs 523 (113) ml·min−1) and filtration fraction (22.4 (3.0) vs 21.8 (3.4)%). Albumin excretion rate (median (range)) declined from 1.1 (0.1–34.7) to 0.5 (0.1–29.9) μg·min−1 (p〈0.01). Changes in glomerular filtration rate (Δ values) were inversely correlated with presentation values (p〈0.001), and positive relationships were observed with Δ effective renal plasma flow (p〈0.01), and Δ glycated haemoglobin (p〈0.05). Type 2 diabetic patients with glomerular filtration rate values at presentation over 120 ml·min−1 demonstrated significant reduction in glomerular filtration rate (n=31; p〈0.001), whilst those with original values less than 120 ml·min−1 remained unchanged (n=45). Glomerular filtration rate, effective renal plasma flow and filtration fraction for the Type 2 diabetic patients remained elevated compared with age-controlled normal subjects (p〈0.01-0.001). Albumin excretion rate at presentation and 6 months were positively correlated with fasting plasma glucose levels (p〈0.05) but not renal haemodynamics. Thus, glomerular filtration rate and albumin excretion rate in newly-presenting Type 2 diabetic patients are influenced by metabolic control. Improved glycaemia for 6 months produces a reduction in glomerular filtration rate, mainly in the younger patients with values greater than 120 ml·min−1 at diagnosis of diabetes. Despite these changes, renal haemodynamic parameters remain elevated compared with age-matched normal subjects.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Increasing concentrations of D-glucose (1 to 25 mM) inhibited somatostatin, thyrotrophin-releasing hormone (TRH) and growth hormone-releasing hormone (GHRH) release from incubated adult rat hypothalami in a stereospecific manner. In contrast, the effects of D- and L-glucose on luteinizing hormone-releasing hormone release were virtually identical. Increasing concentrations of D-glucose also inhibited somatostatin release following depolarization with high K+, but had no obvious effect on depolarization-induced TRH or GHRH release when compared with L-glucose.In conclusion, D-glucose exerts a potent, dose-related modulatory action on the release of rat hypothalamic TRH and GHRH as well as somatostatin in vitro. Further studies are required to establish any physiological relevance of glucose in the modulation of these hypothalamic neuropeptides.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-5233
    Keywords: Key words Segmental tubular reabsorption ; Low molecular weight protein ; Growth hormone ; Microalbuminuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Proximal tubular dysfunction may be implicated in the pathogenesis of diabetic nephropathy. An investigation of proximal tubular function was carried out by assessing proximal tubular sodium reabsorption and low molecular weight protein excretion in a group of patients with type 1 diabetes mellitus. Normoalbuminuric [group A, n=6, albumin excretion rate (AER) mean (range) 4 (0–10) µg/min] and microalbuminuric [group B, n=6, AER 88 (35–198) µg/min] patients with type 1 diabetes were compared with matched controls. Simultaneous lithium and growth hormone (GH) clearance and urinary β 2-microglobulin excretion were assessed. Fasting plasma glucose at the start of the study was [median (range)] 13 (10.2–15.1), 9.3 (5.9–15) and 4.1 (4.0–5.0) mmol/l in groups A, B and controls, respectively, with a mean coefficient of variation during the study of 3.9% (group A) and 5.2% (group B). There was no significant difference in plasma glucose levels between patients in groups A and B. Urinary GH excretion was raised in the patients with microalbuminuria (group B; P〈0.05), although there was no difference in serum GH clearance rate between the patient groups and controls. Urinary GH correlated with β 2-microglobulin in the diabetic subjects (r=0.665, P〈0.05) and with the degree of microalbuminuria in group B patients (r=1, P〈0.01). Urinary GH was also greater than 10 µU, the median value observed in the controls, in 5 of 6 (83%) patients in group A. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) measured by constant infusion of 51Cr-ethylene diamine tetra-acetic acid (EDTA) and I125-para-amino hippuric acid (PAH), respectively, showed relative hyperfiltration in the normoalbuminuric group compared with controls (P〈0.05) and group B (P〈0.05). Absolute proximal reabsorption of sodium and of water (APRNa and APRH2O) was significantly higher in group A patients (P〈0.05). Although GFR was significantly higher in group A patients, no differences were found in fractional proximal reabsorption of sodium and water (FPRNa+H2O) or end proximal delivery between the patient groups and controls. Therefore, the measurement of protein reabsorptive capacity provides a more sensitive marker of renal tubular impairment in type 1 diabetes than sodium/fluid reabsorptive capacity. In patients with microalbuminuria, both glomerular and tubular damage may co-exist. Our results stress the usefulness of markers of renal tubular function in monitoring the course of diabetic nephropathy. This study also shows that assessment of GH clearance has promise as a marker of renal tubular protein reabsorptive capacity.
    Type of Medium: Electronic Resource
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