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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
    ISSN: 1432-0428
    Keywords: 32–33 splet-proinsulin ; Total cholesterol ; high density lipoprotein cholisterol ; plasminogen activator inhibitor ; Blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Standard radioimmunoassay for insulin may substantially overestimate levels of insulin because of cross-reaction with other insulin-like molecules. We have measured concentrations of insulin, intact proinsulin and 32–33 split proinsulin using two-site monoclonal antibody based immunoradiometric assays, and of insulin by a standard radioimmunoassay (“immunoreactive insulin”) in 51 Type 2 (noninsulin-dependent) diabetic subjects in the fasting state. The relationships of these concentrations were sought with those of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, plasminogen activator inhibitor, blood pressure, and indices of body fat distribution. Significant relationships were apparent between concentrations of “immunoreactive insulin” as measured by standard radioimmunoassay and triglyceride (r s=0.42, p〈0.001), total cholesterol (r s=0.25, p=0.038), high density lipoprotein cholesterol (r s=−0.30, p=0.018) and body mass index (r s=0.30, p=0.017), but only the relationships with triglyceride (r s=0.36, p=0.006) and body mass index (r s=0.26, p=0.034) remained significant when concentrations of immunoradiometrically measured insulin were employed. Concentrations of 32—33 split proinsulin, which comprises the major insulin-like molecule in these subjects, correlated positively with triglyceride (r s=0.33, p=0.009), total cholesterol (r s=0.23, p=0.050), and plasminogen activator inhibitor (r s=0.26, p=0.049), and negatively with high density lipoprotein cholesterol (r s=−0.29, p=0.021). Concentrations of “immunoreactive insulin” and immunoradiometric assay insulin showed significant positive correlaion with both systolic (r s=0.24, p=0.044 and r s=0.29, p=0.020 respectively), and diastolic blood pressure (r s=0.48, p〈0.001 and n=0.42, p=0.001 respectively), while those of intact proinsulin and 32–33 split proinsulin correlated only with diastolic blood pressure (r s=0.33, p=0.009 and r s=0.31, p=0.014 respectively). Using multiple regression analysis, and including age, sex, race and body mass index in the analyses, concentrations of intact proinsulin and 32–33 split proinsulin, but not immunoradiometric assay insulin, were significantly related to diastolic blood pressure. When all three molecules were incorporated into a single model, only 32–33 split proinsulin was related to diastolic blood pressure (F-change=6.91, [5,43 degrees of freedom]; p=0.012). Thus, high concentrations of insulin-like molecules are associated with changes in recognised cardiovascular risk factor in patients with Type 2 (non-insulin-dependent) diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Proinsulin ; split proinsulin ; immunoradiometric assay ; Type 2 (non-insulin-dependent) diabetes mellitus ; impaired Beta-cell function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma insulin, intact proinsulin and 32–33 split proinsulin measured by specific immunoradiometric assays and insulin and C-peptide measured by radioimmunoassay were measured during a constant infusion of glucose test in ten diet-treated subjects with a history of Type 2 (non-insulin-dependent) diabetes (termed diabetic subjects), mean fasting plasma glucose 6.0 ± 1.0 mmol/l (mean ± SD), and 12 non-diabetic control subjects. Immunoreactive insulin concentrations measured by radioimmunoassay were 33 higher than insulin and 16 % higher than the sum of insulin and its precursors by immunoradiometric assay. The diabetic and non-diabetic subjects had similar fasting concentrations of insulin, intact proinsulin and 32–33 split proinsulin. The ratio of fasting intact proinsulin to total insulin was greater in the diabetic than the non-diabetic group 12.0 % (6.8–21.0 %, 1 SD range) and 6.3 % (4.0–9.8 %), respectively,p 〈 0.01), though the groups overlapped substantially. After glucose infusion, diabetic and non-diabetic subjects had similar intact proinsulin concentrations (geometric mean 4.9 and 5.2 pmol/l, respectively), but the diabetic group had impaired insulin secretion by immunoradiometric assay (geometric means 55 and 101 pmol/1,p 〈 0.05) or by radioimmunoassay C-peptide (geometric means 935 and 1410 pmol/1,p 〈 0.05), though not by radioimmunoassay insulin (87 and 144 pmol/1,p = 0.12), respectively. Individual immunoradiometric assay insulin responses to glucose expressed in terms of obesity were subnormal in nine of ten diabetic subjects. Radioimmunoassay insulin and C-peptide gave less complete discrimination ( subnormal responses in six of ten and eight of ten, respectively). Thus, raised proinsulin and proinsulin:total insulin ratio are not necessarily a feature of mild diet-treated Type 2 diabetic patients with subnormal insulin responses to glucose.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; hypertension ; hyperlipidaemia ; syndrome X ; reduced fetal growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two follow-up studies were carried out to determine whether lower birthweight is related to the occurrence of syndrome X — Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia. The first study included 407 men born in Hertfordshire, England between 1920 and 1930 whose weights at birth and at 1 year of age had been recorded by health visitors. The second study included 266 men and women born in Preston, UK, between 1935 and 1943 whose size at birth had been measured in detail. The prevalence of syndrome X fell progressively in both men and women, from those who had the lowest to those who had the highest birthweights. Of 64-year-old men whose birthweights were 2.95 kg (6.5 pounds) or less, 22% had syndrome X. Their risk of developing syndrome X was more than 10 times greater than that of men whose birthweights were more than 4.31 kg (9.5 pounds). The association between syndrome X and low birthweight was independent of duration of gestation and of possible confounding variables including cigarette smoking, alcohol consumption and social class currently or at birth. In addition to low birthweight, subjects with syndrome X had small head circumference and low ponderal index at birth, and low weight and below-average dental eruption at 1 year of age. It is concluded that Type 2 diabetes and hypertension have a common origin in sub-optimal development in utero, and that syndrome X should perhaps be re-named “the small-baby syndrome”.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 157 (1997), S. S7 
    ISSN: 1432-1076
    Keywords: Key words Fetal growth ; Blood pressure ; Glucose tolerance ; Programming ; HPA axis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is now a large body of evidence to support the hypothesis that events in fetal life permanently alter the structure or function of an individual, programming later adult disease. Reduced birth weight is associated with higher blood pressure in childhood and adult life, and thinness at birth with glucose intolerance and non-insulin dependent diabetes mellitus. Programming of the hypothalamo-pituitary-adrenal (HPA) axis is an attractive hypothesis linking fetal experience and later disease, as an excess of glucocorticoids may be associated with hypertension and glucose intolerance. Moreover, animal data support this hypothesis. Exposing fetal rats to glucocorticoid reduces birth weight and leads to raised blood pressure, as well as to alterations in the HPA axis. Data on the long-term effects of exposure to glucocorticoids in human subjects are limited. Recently, however, reduced size at birth was found to be associated with higher fasting 9 a.m. plasma cortisol concentrations in adults. Raised plasma cortisol concentrations were, in turn, associated with higher blood pressure, and inversely related to measures of glucose tolerance. Conclusion Programming of the HPA axis by events in fetal life may be one of the mechanisms linking reduced size at birth with raised blood pressure and glucose intolerance in later life. Studies of the effects of antenatal and neonatal dexamethasone administration on later blood pressure and glucose tolerance may be warranted.
    Type of Medium: Electronic Resource
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