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  • insulin  (7)
  • Type 2 (non-insulin-dependent) diabetes mellitus  (3)
  • fetal growth  (3)
  • 1
    ISSN: 1432-0428
    Schlagwort(e): Indirect two-site immunoradiometric assay ; human proinsulin ; insulin ; C-peptide ; diabetes ; insulinoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary An indirect two-site immunoradiometric assay is described for the measurement of human proinsulin in plasma. Polyethylene tubes coated with purified guinea-pig antibodies to insulin were used to extract proinsulin and insulin from plasma. Rabbit antibody to human C peptide was then added to react with the C-peptide moiety of the bound proinsulin. The uptake of this antibody was measured by the subsequent binding of125I-sheep antibody to rabbit IgG. The binding of radioactivity to the tubes was a function of the proinsulin concentration in the sample. The sensitivity of the assay was 0.006 pmol/ml. Only 200 μl of plasma was required in the assay and the125I-labelled antibody was produced from readily available reagents. The polyethylene tubes remained stable for at least 5 months after coating. The mean fasting proinsulin level was 0.009 pmol/ml in sixteen normal subjects and 0.025 pmol/ml in twelve maturity onset diabetics. Oral glucose produced an 8 fold increase in proinsulin concentration but a decline in the plasma proinsulin/insulin molar ratio. Four patients with insulinoma had extremely elevated proinsulin levels and proinsulin/insulin ratios.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): Type 2 (non-insulin-dependent) diabetes mellitus ; impaired glucose tolerance ; glucose tolerance ; oral glucose tolerance test ; epidemiology ; height ; body mass index ; waist/hip ratio
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-0428
    Schlagwort(e): Proinsulin ; split proinsulin ; immunoradiometric assay ; Type 2 (non-insulin-dependent) diabetes mellitus ; impaired Beta-cell function
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-0428
    Schlagwort(e): Type 2 (non-insulin-dependent) diabetes mellitus ; hypertension ; hyperlipidaemia ; syndrome X ; reduced fetal growth
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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”.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 37 (1994), S. 592-596 
    ISSN: 1432-0428
    Schlagwort(e): NIDDM ; insulin secretion ; fetal growth ; programming
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-0428
    Schlagwort(e): Proinsulin ; insulin ; C-peptide ; identical twins ; Type 1 (insulin-dependent) diabetes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Glucose tolerance and insulin secretion were studied in two groups of non-diabetic identical twins of recently-diagnosed Type 1 (insulin-dependent) diabetic patients: (1) a group of 5 twins with islet cell antibodies, and (2) a group of 6 twins without. Despite similar fasting glucose, insulin and C-peptide concentrations both groups of twins had significantly higher fasting proinsulin concentrations than the control group (p〈0.05). The twins with complement-fixing islet cell antibodies had reduced glucose tolerance and clearance, whilst the twins without islet cell antibodies did not. Neither group of twins showed any abnormality in insulin, C-peptide or proinsulin response to oral or intravenous glucose. We conclude that increased fasting proinsulin levels precede abnormalities of insulin secretion, and are an early indication of minor B-cell damage in these twins irrespective of their risk of developing diabetes.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-0428
    Schlagwort(e): Proinsulin ; insulin ; insulin secretion ; non-insulin-dependent diabetes mellitus ; epidemiology ; follow-up study
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Insulin resistance and impaired insulin secretion are thought to be the primary defects in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Disproportionately increased proinsulin relative to insulin levels are suggested to be an early indicator of a failing pancreas. We examined the relationship of fasting specific insulin, proinsulin, and 32, 33 split proinsulin concentrations, and the proinsulin: insulin ratio to the risk of developing NIDDM 3.5 years later in 65–74-year-old non-diabetic Finnish subjects participating in a populationbased study (n=892) on diabetes and heart disease. Altogether 69 subjects developed NIDDM over a 3.5-year follow-up (cases). The cases were compared to randomly-selected gender-matched control subjects (n=69) and control subjects matched for gender, glucose tolerance status (normal or impaired), and body mass index (n=69). There were no differences in insulin concentrations between cases and random or matched control subjects [median and interquartile range; 123 (77–154), 108 (74–143), 118 (83–145) pmol/l, p=0.271]. Random control subjects had lower proinsulin and 32,33 split proinsulin concentrations and split proinsulin: insulin ratios compared to cases [5.7 (3.8–9.0) vs 7.3 (4.8–10.0) pmol/l, p=0.005; 7.3 (4.5–13.0) vs 10.4 (7.1–18.0) pmol/l, p=0.002; 0.073 (0.057–0.110) vs 0.097 (0.060–0.135), p=0.003]. Matched control subjects had lower proinsulin concentrations and proinsulin: insulin ratios compared to cases [5.9 (4.0–7.7) vs 7.3 (4.8–10.0) pmol/l, p=0.019; 0.048 (0.035–0.071) vs 0.064 (0.045–0.100), p=0.008]. When cases were compared to matched control subjects a 1 SD increase in baseline proinsulin: insulin ratio was associated with a 1.37-fold risk (p=0.020) of developing diabetes. Moreover, this association was independent of fasting glucose concentration at baseline. Thus, in elderly prediabetic subjects disproportionately increased proinsulin concentration, an indicator of defective insulin secretion, is associated with conversion to diabetes over a short time period.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-0428
    Schlagwort(e): Keywords Insulin resistance ; fetal growth ; non-insulin-dependent diabetes mellitus ; desaturase activity.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-0428
    Schlagwort(e): Keywords Proinsulin ; insulin ; insulin secretion ; insulin resistance.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Aims/hypothesis. Proinsulin concentrations are increased relative to insulin concentrations in subjects with Type II (non-insulin-dependent) diabetes mellitus. This could be secondary to hyperglycaemia or insulin resistance or due to a defect in insulin secretion. Methods. We investigated the association between fasting insulin, intact proinsulin and the intact proinsulin: insulin ratio with insulin sensitivity, estimated by a frequently sampled intravenous glucose tolerance test and the minimal model and with acute insulin response (AIR) in 182 newly diagnosed Type II diabetic subjects aged 40 to 69 years. None of the subjects was receiving hypoglycaemic medication. Results. Insulin sensitivity correlated inversely with fasting insulin (r s = –0.42) and intact proinsulin (r s = –0.32) (p 〈 0.001). The intact proinsulin:insulin ratio was not correlated with insulin sensitivity. AIR correlated positively with intact proinsulin (r s = 0.23) and inversely with the intact proinsulin:insulin ratio (r s = –0.29, p 〈 0.001). Fasting glucose correlated positively with intact proinsulin (r s = 0.34) and the intact proinsulin:insulin ratio (r s = 0.24, p 〈 0.001). The intact proinsulin:insulin ratio increased by decreasing AIR (quartiles of AIR from high to low: 7.8, 8.2, 9.7 and 12.1 %, p 〈 0.001). This association was independent of age, sex, ethnicity, body mass index, fasting glucose, and insulin sensitivity. Conclusion/interpretation. Insulin resistance (low insulin sensitivity) was not related to the intact proinsulin:insulin ratio in subjects with Type II diabetes. In contrast, both low AIR and high fasting glucose concentrations were associated with a disproportionate increase in proinsulin concentration. These results suggest that increased intact proinsulin:insulin ratio is a marker of a defect in insulin secretion in Type II diabetic subjects. [Diabetologia (1999) 42: 1060–1066]
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-0428
    Schlagwort(e): Key words Proinsulin ; insulin ; insulin secretion ; non-insulin-dependent diabetes mellitus ; epidemiology ; follow-up study.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Insulin resistance and impaired insulin secretion are thought to be the primary defects in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Disproportionately increased proinsulin relative to insulin levels are suggested to be an early indicator of a failing pancreas. We examined the relationship of fasting specific insulin, proinsulin, and 32, 33 split proinsulin concentrations, and the proinsulin: insulin ratio to the risk of developing NIDDM 3.5 years later in 65–74-year-old non-diabetic Finnish subjects participating in a population-based study (n = 892) on diabetes and heart disease. Altogether 69 subjects developed NIDDM over a 3.5-year follow-up (cases). The cases were compared to randomly-selected gender-matched control subjects (n = 69) and control subjects matched for gender, glucose tolerance status (normal or impaired), and body mass index (n = 69). There were no differences in insulin concentrations between cases and random or matched control subjects [median and interquartile range; 123 (77–154), 108 (74–143), 118 (83–145) pmol/l, p = 0.271]. Random control subjects had lower proinsulin and 32,33 split proinsulin concentrations and split proinsulin: insulin ratios compared to cases [5.7 (3.8–9.0) vs 7.3 (4.8–10.0) pmol/l, p = 0.005; 7.3 (4.5–13.0) vs 10.4 (7.1–18.0) pmol/l, p = 0.002; 0.073 (0.057–0.110) vs 0.097 (0.060–0.135), p = 0.003]. Matched control subjects had lower proinsulin concentrations and proinsulin: insulin ratios compared to cases [5.9 (4.0–7.7) vs 7.3 (4.8–10.0) pmol/l, p = 0.019; 0.048 (0.035–0.071) vs 0.064 (0.045–0.100), p = 0.008]. When cases were compared to matched control subjects a 1 SD increase in baseline proinsulin: insulin ratio was associated with a 1.37-fold risk (p = 0.020) of developing diabetes. Moreover, this association was independent of fasting glucose concentration at baseline. Thus, in elderly prediabetic subjects disproportionately increased proinsulin concentration, an indicator of defective insulin secretion, is associated with conversion to diabetes over a short time period. [Diabetologia (1995) 38: 1176–1182]
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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