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  • 1
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; vitamin D ; vitamin D deficiency ; total insulin ; specific insulin ; proinsulin ; 32,33 split proinsulin ; C-peptide ; glucose intolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vitamin D deficiency reduces insulin secretion and still occurs in East London Asians in whom the prevalence of diabetes mellitus is at least four times that of Caucasians. Vitamin D status was assessed in 44 of 65 non-diabetic subjects ‘at risk’ of diabetes (spot blood glucose level 〉6.0 mmol/l 〈2 h post cibum, or 〉4.6 mmol/l 〉2 h post cibum on two separate occasions) and in 15 of 60 age and sex-matched ‘low-risk’ control subjects who attended for oral glucose tolerance test (OGTT) after screening of 877 omnivorous subjects not known to have diabetes. It was found that 95% of at-risk and 80% of low-risk subjects were vitamin D deficient (serum 25-hydroxy-vitamin D 〈11 ng/ml). Diabetes was present in 16, impaired glucose tolerance in 12 and normoglycaemia in 19 at-risk subjects, impaired glucose tolerance in 2, and normoglycaemia in 13 low-risk subjects. Correlations of 30-min OGTT blood glucose, specific insulin and C-peptide levels with 25-hydroxy-vitamin D concentrations in 44 at-risk subjects were −0.31 (p=0.04), 0.59 (p=0.0001) and 0.44 (p=0.006). In 15 ‘not-at-risk’ subjects 30-min OGTT specific insulin and C-peptide levels correlated with 25-hydroxy-vitamin D, r=0.39 (p=0.04) and 0.16 (p=0.43), respectively. Serum alkaline phosphatase concentration was higher in at-risk than not-at-risk subjects (59.6 vs 46.5 IU/l, p=0.012); corrected calcium concentrations were comparable (2.38 vs 2.39 mmol/l, p=0.7). Following treatment with 100,000 IU vitamin D by i.m. injection, specific insulin, C-peptide [30 min on OGTT] and 25-hydroxy-vitamin D concentrations had risen 8–12 weeks later [means±SD] from 57±62 to 96.2±82.4 mU/l [p=0.0017], 1.0±0.4 to 1.7±0.8 pmol/ml [p=0.0001] and 3.6±1.8 to 13.5±7.4 ng/ml [p=0.0001], (but not to low-risk group values of 179±89 mU/l, 2.7±1.14 pmol/ml and 8.16±6.4 ng/ml), respectively. Both total serum alkaline phosphatase and corrected calcium concentrations rose following vitamin D treatment in the at-risk subjects by 11.1±8.22 (from 44 to 55 IU/l) and 0.15±0.18, (2.43 to 2.57 mmol/l), respectively (p=0.004). Abnormal glucose tolerance was unchanged by vitamin D treatment. The value of early and sustained repletion with vitamin D in diabetes prophylaxis should be examined in communities where vitamin D depletion is common.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; insulin ; sulphonylurea receptors ; islets ; glibenclamide ; secretory granule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sulphonylureas stimulate insulin secretion by binding to a receptor in the pancreatic beta-cell plasma membrane resulting in inhibition of ATP-sensitive K+ channels, membrane depolarization and thus influx of Ca2+ through voltage-dependent Ca2+ channels. Sulphonylureas can also induce hormone release at fixed membrane potentials without Ca2+ entry suggesting that these drugs may have other modes of action. We have determined whether different forms of sulphonylurea-binding proteins are present in insulin-secreting cells and their subcellular localization by density gradient centrifugation. Binding studies using [3H]-glibenclamide showed that islet and insulinoma membranes contained a single high affinity sulphonylurea binding site (Kd = 1 nmol/l). Photo-crosslinking of the drug to the membranes resulted in labelling of two proteins with apparent molecular weights of 170 and 140 kDa. The same analyses of insulinoma subcellular fractions showed that the majority (〉90%) of binding proteins were localized to intracellular membranes with only minor levels (〈10%) on plasma membranes. The 170 kDa sulphonylurea binding protein was present in both plasma and granule membrane fractions whereas the 140 kDa form was not present in the plasma membrane fraction. The differences in the molecular forms and subcellular distribution of the receptor are consistent with sulphonylureas having multiple sites of action in the pancreatic beta cell.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords Insulin resistance ; fetal growth ; non-insulin-dependent diabetes mellitus ; desaturase activity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Numerous studies show an association between poor fetal growth and adult insulin resistance. Recent studies have shown relation between the long chain polyunsaturated fatty acid composition of skeletal muscle membranes and insulin sensitivity. More detailed analysis has indicated that the activity of Δ5 desaturase is inversely correlated to insulin resistance. The amount of docosahexaenoic acid (C22:6n3) is also thought to play a part in determining insulin sensitivity. The purpose of this study was to test the hypothesis that early growth retardation in the rat, as a result of maternal protein restriction, would lead to alterations in desaturase activities similar to those observed in human insulin resistance. There were no differences in phospholipid fatty acid composition in liver or muscle from control and low protein rats. In both muscle and liver the ratio of docosahexaenoic acid to docosapentaenoic acid was, however, reduced in low protein offspring. Direct measurement of Δ5 desaturase activity in hepatic microsomes showed a reduction (p 〈 0.03) in the low protein offspring which was negatively corrrelated (r = – 0.855) with fasting plasma insulin. No correlation was observed in controls. These results show that it is possible to programme the activity of key enzymes involved in the desaturation of long chain polyunsaturated fatty acids. This is possibly a mechanism linking fetal growth retardation to insulin resistance. [Diabetologia (1998) 41: 1337–1342]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Impaired glucose tolerance ; non-insulin-dependent diabetes mellitus ; fetal growth ; ponderal index at birth ; placental weight to birthweight ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A follow-up study was carried out to determine whether reduced fetal growth is associated with the development of impaired glucose tolerance in men and women aged 50 years. Standard oral glucose tolerance tests were carried out on 140 men and 126 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size at birth had been measured in detail. Those subjects found to have impaired glucose tolerance or non-insulin-dependent diabetes mellitus had lower birthweight, a smaller head circumference and were thinner at birth. They also had a higher ratio of placental weight to birthweight. The prevalence of impaired glucose tolerance or diabetes fell from 27% in subjects who weighed 2.50 kg (5.5 pounds) or less at birth to 6% in those who weighed more than 3.41 kg (7.5 pounds) (p 〈 0.002 after adjusting for body mass index). Plasma glucose concentrations taken at 2-h in the glucose tolerance test fell progressively as birthweight increased (p 〈 0.004), as did 2-h plasma insulin concentrations (p 〈 0.001). The trends with birthweight were independent of duration of gestation and must therefore be related to reduced rates of fetal growth. These findings confirm the association between impaired glucose tolerance in adult life and low birthweight previously reported in Hertfordshire (UK), and demonstrate it in women as well as men. It is suggested that the association reflects the long-term effects of reduced growth of the endocrine pancreas and other tissues in utero. This may be a consequence of maternal undernutrition.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; impaired glucose tolerance ; hypertriglyceridaemia ; hyperinsulinaemia ; non-esterified fatty acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Although plasma insulin and triglyceride concentrations are positively correlated in many studies, the relationships between insulin resistance, insulin secretion and hypertriglyceridaemia remain unclear. To study these associations, subjects between the ages of 40 and 64 were randomly selected from a general practice register and invited to attend for a standard oral glucose tolerance test for measurement of insulin, triglyceride and non-esterified fatty acid concentrations. The study comprised 1122 subjects who were not previously known to have diabetes and who completed the test. Using the World Health Organisation criteria, 51 subjects were classified to have non-insulin-dependent diabetes mellitus, 188 had impaired glucose tolerance and 883 subjects had normal glucose tolerance. Triglyceride concentrations in subjects with glucose intolerance were elevated compared to those in control subjects, even after adjustment for age, obesity and gender (p〈0.001 for subjects with diabetes and p〈0.01 for those with impaired glucose tolerance compared to normal subjects). In separate multiple regression analyses for males and females, the most important determinants of the plasma triglyceride concentration were the area under the non-esterified fatty acid suppression curve (p〈0.001 in both genders) and the waist-hip ratio (p〈0.001 for men and 〈0.01 for women). The fasting insulin concentration was independently associated with triglyceride concentration in women only (p〈0.01). The most important determinant of the area under the non-esterified fatty acid suppression curve in men was the 30-min insulin increment, a measure of insulin secretion, (p〈0.001) whereas for women age (p〈0.001) and the body mass index (p〈0.01) were the most important.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. S162 
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; impaired glucose tolerance ; immunoassay ; pro-insulin-related molecules ; birth weight
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Improvements in the specificity and sensitivity of assays for insulin-related molecules in the circulation have proved to be necessary and informative in studies of the pathogenesis of non-insulin-dependent diabetes (NIDDM). Of particular interest has been the close relationship between increases in des 31,32 split proinsulin and susceptibility to loss of glucose tolerance and the insulin resistance syndrome. It is suggested that the analogy can be drawn between this measurement and the measurement of HbA1c. The amount of this partially processed precursor of insulin in the circulation indicates the degree of glucose stimulus applied to the beta cell combined with the inherent capacity of the insulin secretory system to respond. Further improvements of the sensitivity and specificity of the assay of proinsulin related molecules are desirable. Deterioration of the early insulin response to oral glucose is a major feature of the loss of glucose tolerance associated with the transition from normal to impaired glucose tolerance and to NIDDM. The extent to which this loss of insulin secretion reflects a major predisposing factor in the aetiology of this type of diabetes or is secondary to glucose toxicity or amyloid accumulation remains to be determined. A relationship between birth weight and impaired glucose tolerance, NIDDM and the insulin resistance syndrome has now been observed in two populations in the UK, in Mexican Americans and in Pima Indians. It is therefore reproducible and applicable to widely differing populations. Much further research is indicated to determine, amongst many questions, how much diabetes is associated with this link and what factors explain it.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. 592-596 
    ISSN: 1432-0428
    Keywords: NIDDM ; insulin secretion ; fetal growth ; programming
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent studies suggest that NIDDM is linked with reduced fetal and infant growth. Observations on malnourished infants and studies of experimental animals exposed to protein energy or protein deficiency in fetal or early neonatal life suggest that the basis of this link could lie in the detrimental effects of poor early nutrition on the development of the beta cells of the islets of Langerhans. To test this hypothesis we have measured insulin secretion following an IVGTT in a sample of 82 normoglycaemic and 23 glucose intolerant subjects who were born in Preston, England, and whose birthweight and body size had been recorded at birth. The subjects with impaired glucose tolerance had lower first phase insulin secretion than the normoglycaemic subjects (mean plasma insulin concentrations 3 min after intravenous glucose 416 vs 564 pmol/l, p=0.04). Insulin secretion was higher in men than women (601 vs 457 pmol/l, P=0.02) and correlated with fasting insulin level (p=0.04). However, there was no relationship between insulin secretion and the measurements of prenatal growth in either the normoglycaemic or glucose intolerant subjects. These results argue against a major role for defective insulin secretion as a cause of glucose intolerance in adults who were growth retarded in pre-natal life.
    Type of Medium: Electronic Resource
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