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  • 1
    ISSN: 1432-0428
    Keywords: Indirect two-site immunoradiometric assay ; human proinsulin ; insulin ; C-peptide ; diabetes ; insulinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Proinsulin ; insulin ; C-peptide ; identical twins ; Type 1 (insulin-dependent) diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words 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. [Diabetologia (1995) 38: 1239–1245]
    Type of Medium: Electronic Resource
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  • 4
    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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