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  • 1
    Electronic Resource
    Electronic Resource
    Fetal growth and impaired glucose tolerance in men and women (1993)
    Springer
    Diabetologia 36 (1993), S. 225-228 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00399954
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  • 2
    Electronic Resource
    Electronic Resource
    Immunoradiometric assay of insulin, intact proinsulin and 32–33 split proinsulin and radioimmunoassay of insulin in diet-treated Type 2 (non-insulin-dependent) diabetic subjects (1992)
    Springer
    Diabetologia 35 (1992), S. 469-474 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF02342446
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  • 3
    Electronic Resource
    Electronic Resource
    Assessment of proinsulin's effects on intermediary metabolism using the forearm technique in normal man (1993)
    Springer
    Acta diabetologica 30 (1993), S. 29-35 
    Details
    ISSN: 1432-5233
    Keywords: Forearm ; Lactate ; Man ; Proinsulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have compared the effects of human proinsulin and insulin on forearm metabolism. Seven normal, non-obese subjects were infused with 386 pmol/kg per hour of proinsulin and 180 pmol/kg per hour of insulin using the euglycaemic clamp technique. Glucose appearance and utilization rates were quantified using a primed continuous infusion of [6′,6′-2H2]glucose. Mean blood glucose was 4.1±0.1 and 4.1±0.2 mmol/l during proinsulin and insulin infusions respectively. Basal insulin concentrations increased from 0.02±0.01 to 0.25±0.03 nmol/l. The proinsulin infusion was chosen to give steady-state levels approximately 20-fold higher on a molar basis than those of insulin, based on previous findings that proinsulin has only 5% the biological potency of insulin. Basal proinsulin concentrations increased from 0.003 to 5.4±0.3 nmol/l. Hepatic glucose production was suppressed similarly during the last hour of each hormone infusion: 0.07±0.16 (proinsulin, P), and 0.01±0.13 (insulin, I) mg/kg per minute. Glucose disposal, however, was significantly increased during the final hour of the insulin infusion: 4.7±0.4 (I) and 3.4±0.2 (P) mg/kg per minute (P=0.025). Net forearm glucose uptake (FGU) increased by a greater amount during insulin compared with proinsulin infusion: 1.44±0.02 (I) and 0.71±0.01 (P) μmol/100 ml forearm per minute (P〈0.02). There was a small but significant net drop in arterialized blood lactate and pyruvate concentrations during proinsulin compared with insulin infusion: lactate −43±29 (P) and +63±35 (I) μmol/l (P〈0.01); pyruvate −8±3 (P) and +6±2 (I) μmol/l (P〈0.02). Arterialized blood alanine concentrations were similar during both series of hormone infusions. Forearm production and arterialized concentrations of glycerol were suppressed by equal amounts during the last hour of each hormone infusion. Despite greater FGU during insulin infusion, forearm production of lactate, pyruvate and alanine were similar during the last hour of each glucose clamp. These results indicate that in overnight fasted normal man: (1) proinsulin may have a preferential effect on the liver compared with muscle in terms of glucose handling; (2) proinsulin is less effective in stimulating FGU than is insulin; (3) from calculation of carbon flux across the forearm, proportionally less glucose was oxidized or stored during infusion of proinsulin compared with insulin; (4) proinsulin has similar effects on forearm lipolysis compared with insulin; (5) proinsulin may have a differential effect on splanchnic lactate metabolism compared with insulin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00572871
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    Paper (German National Licenses)
    Fulltext
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