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  • 1
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; impaired glucose tolerance ; glucose tolerance ; oral glucose tolerance test ; epidemiology ; height ; body mass index ; waist/hip ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a prospective study concerning the pathogenesis of impaired glucose tolerance and Type 2 (non-insulindependent) diabetes mellitus, 346 subjects with no clinical history of diabetes were given a standard 75 g oral glucose tolerance test. The expected positive associations between 120-min plasma glucose concentration and age and body mass index were observed in both sexes and between 120-min plasma glucose and waist/hip ratio in male subjects. An unexpected negative correlation was found between 120-min plasma glucose and height in both sexes (r = − 0.23, (95% confidence interval, − 0.38− − 0.07) p〈0.007 for male subjects and r = − 0.24, (− 0.37− − 0.11) p〈0.006 for female subjects). These negative associations with height remained significant after controlling for age and body mass index in male subjects but not in female subjects. In the latter a highly significant negative relationship of height with age was recorded (r = − 0.33, (− 0.45− − 0.20) p〈0.0001). Comparison between individuals with impaired glucose tolerance and control subjects matched for sex, age and body mass index showed that subjects with impaired glucose tolerance are significantly shorter. Mean (± SEM) height in the male subjects with impaired glucose tolerance (n = 29) was 173.4 ± 1.1 cm vs 176.9 ± 1.3 cm in control subjects, p = 0.02. In the female subjects(n = 39)mean(±SEM)height was 159.4±1.0 cm vs 162.4±1.0 cm in control subjects, p = 0.02. The negative relationship between height and glucose tolerance is a new epidemiological observation which has not been previously reported. One possible reason for this is that the most commonly used anthropometric index, body mass index, eliminates height as an independent analytical variable.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 36 (1993), S. 974-974 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. 592-596 
    ISSN: 1432-0428
    Keywords: Key words 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 prenatal life. [Diabetologia (1994) 37: 592–596]
    Type of Medium: Electronic Resource
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  • 4
    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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  • 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 38 (1995), S. 124-124 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Key words Hypertriglyceridaemia ; non-esterified fatty acid ; ischaemic heart disease ; smoking.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate causes of increased triglyceride concentrations in subjects with normal glucose tolerance (determined by oral glucose tolerance testing using World Health Organization criteria) 883 healthy subjects (389 men and 494 women) between 40 and 65 years of age were studied. Subjects were divided by gender into four groups according to 120-min glucose concentrations. Individuals in the highest quartile of glucose concentration had the highest mean triglyceride concentrations (p 〈 0.0001) and highest mean non-esterified fatty acid (NEFA) concentrations (p 〈 0.0001). There was also a clustering of cardiovascular risk factors normally associated with the insulin resistance syndrome in subjects in this group. Regression analysis showed that the most important determinants of triglyceride levels were smoking (men p = 0.001, women p = 0.005), waist:hip ratio (men p = 0.01, women p 〈 0.001) and NEFA suppression (men p = 0.02, women p = 0.005). NEFAs suppressed 16.7 % in women compared to 2.4 % in men during the first 30 min of the oral glucose tolerance test (p 〈 0.001). These results show that a clustering of cardiovascular risk factors associated with decreased NEFA suppression occurs in a sub-group of subjects with normal glucose tolerance and that the pattern of NEFA suppression differs between men and women. [Diabetologia (1995) 38: 1358–1366]
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Hypertriglyceridaemia ; non-esterified fatty acid ; ischaemic heart disease ; smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate causes of increased triglyceride concentrations in subjects with normal glucose tolerance (determined by oral glucose tolerance testing using World Health Organization criteria) 883 healthy subjects (389 men and 494 women) between 40 and 65 years of age were studied. Subjects were divided by gender into four groups according to 120-min glucose concentrations. Individuals in the highest quartile of glucose concentration had the highest mean triglyceride concentrations (p〈0.0001) and highest mean non-esterified fatty acid (NEFA) concentrations (p〈0.0001). There was also a clustering of cardiovascular risk factors normally associated with the insulin resistance syndrome in subjects in this group. Regression analysis showed that the most important determinants of triglyceride levels were smoking (men p=0.001, women p=0.005), waist:hip ratio (men p=0.01, women p〈0.001) and NEFA suppression (men p=0.02, women p=0.005). NEFAs suppressed 16.7% in women compared to 2.4% in men during the first 30 min of the oral glucose tolerance test (p〈0.001). These results show that a clustering of cardiovascular risk factors associated with decreased NEFA suppression occurs in a sub-group of subjects with normal glucose tolerance and that the pattern of NEFA suppression differs between men and women.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Key words 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. [Diabetologia (1995) 38: 277–282]
    Type of Medium: Electronic Resource
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  • 10
    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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