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  • 1
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; insulin secretion ; Beta-cell function ; glucose tolerance test ; insulin resistance ; obesity ; hyperglycaemic clamp ; euglycaemic clamp ; plasma insulin ; plasma C-peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma insulin or C-peptide response to a 90-min constant glucose infusion 5 mg · kg ideal body weight−1·min−1 provides Beta-cell assessment comparable to more intensive methods. In 14 diet-treated Type 2 (non-insulin-dependent) diabetic subjects and 12 non-diabetic subjects, plasma insulin and C-peptide concentrations gave near linear plots against simultaneous glucose values. The ‘glucose-insulin and glucose-C-peptide vectors’ (G-I and G-C vectors), could be extrapolated to predict insulin and C-peptide levels during a 12 mmol/l hyperglycaemic clamp. Predicted concentrations correlated with clamp concentrations, r = 0.94 and r = 0.98 respectively, p〈0.001, validating the vectors as empirical glucose dose-response curves. The vector slopes correlated highly with % Beta, a mathematical model-derived measure of Beta-cell function using constant infusion of glucose model assessment, Spearman r = 0.95 and 0.93 for insulin and C-peptide, respectively. G-I vector slopes in 21 diet-treated Type 2 diabetic subjects with fasting glucose (mean +1 SD) 7.5±2,3 mmol/1, were lower than in 28 non-diabetic subjects, (geometric mean, 1 SD range, 8.4 pmol/mmol (3.3–21.0) and 25.1 pmol/mmol (14.3–44.1), p〈0.001, respectively), indicating an impaired Beta-cell response. The G-I vector slopes correlated with obesity in both groups (r = 0.54 p〈0.02 and 0.72, p〈0.001 respectively), and, in 15 non-diabetic subjects, correlated inversely with insulin sensitivity as measured by a euglycaemic clamp (r = −0.66, p〈0.01).Thus,Beta-cell function needs to be interpreted in relation to obesity/insulin resistance and, taking obesity into account, only 4 of 21 diabetic patients had Betacell function (G-I vector slope) in the non-diabetic range. The fasting plasma glucose in the diabetic subjects correlated inversely with the obesity-corrected G-I and G-C vector slopes (partial r = −0.57, p 〈0.01 and −0.86, p〈0.001, respectively). The insulin or C-peptide response to the glucose infusion provides a direct empirical measure of the Beta-cell function, which can be interpreted in relation to obesity or to insulin resistance to assess underlying pancreatic responsiveness.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Growth hormone ; Type 1 (insulin-dependent) diabetes mellitus ; pulsatile and continuous growth hormone ; insulin requirements ; ketones ; B-hydroxybutyrate ; non-esterified fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma growth hormone profiles in adolescents with Type 1 (insulin-dependent) diabetes mellitus are characterized by both increases in pulse amplitude and higher baseline concentrations. To determine which of these abnormalities adversely affect metabolic control, we studied six young adults overnight on three occasions. On each night somatostatin (50–100 μg·m2−1·h−1) and glucagon (1ng· kg−1·min−1) were infused continuously and 18mU/kg of growth hormone was given as either: three discrete pulses of 6 mU·kg−1· h−1 at 180-min intervals or a 12-h infusion (1.5 mU·kg−1· h−1) or buffer solution only on a control night. Euglycaemia was maintained by an insulin-varying clamp. Blood samples were taken every 15 min for glucose and growth hormone and every hour for intermediate metabolites and non-esterified fatty acids. Comparable normoglycaemic conditions were achieved on all three nights. Growth hormone levels achieved (mean±SEM) on study nights were: 32.8±2.2 mU/l (peak level during growth hormone pulses); 9.8± 0.8 mU/l (continuous growth hormone) and 1.1±0.3 mU/l (control level). Pulsatile growth hormone administration led to an increase in insulin requirements (mean±SEM: 0.17±0.03 vs control 0.09±0.01 mU·kg−1· min−1, p 〈 0.05) whereas insulin requirements following continuous growth hormone administration were unchanged. Cross-correlation confirmed an increase in insulin requirements occurring 135 min after a growth hormone pulse (r=0.21, p 〈 0.001). Growth hormone administration (continuous and pulsatile) led to a significant increase in B-hydroxybutyrate levels compared to the control night: 0.21±0.01 mmol/l (mean±SEM), 0.29±0.01 mmol/l, 0.08±0.01 mmol/l (p〈 0.001) during the night with pulsatile growth hormone, continuous growth hormone and control respectively. Mean plasma non-esterified fatty acids were also increased following growth hormone administration: 0.94±0.04 mmol/l (mean±SEM), 1.09±0.07 mmol/l, 0.61±0.05 mmol/l (p〈0.003), during the night with pulsatile growth hormone, continuous growth hormone and control respectively. It appears that the pulsatile and baseline growth hormone signals have contrasting metabolic effects in young adults with Type 1 diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; insulin requirements ; insulin-like growth factor I ; growth hormone ; adolescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Type 1 (insulin-dependent) diabetes mellitus in adolescence is associated with reduced levels of insulin-like growth factor I, elevated growth hormone concentrations and insulin resistance. In order to determine whether restoring insulin-like growth factor I levels to normal might lead to a reduction in growth hormone levels and insulin requirements, we undertook a double-blind placebo controlled study of a single s. c. dose of recombinant insulin-like growth factor I (40 μg/kg body weight) in nine late pubertal subjects with Type 1 diabetes. After administration of placebo or insulin-like growth factor I at 18.00 hours, a variable rate insulin infusion was used to maintain euglycaemia overnight. Plasma insulin-like growth factor I, growth hormone, free insulin, and intermediate metabolite concentrations were monitored throughout the study. Recombinant insulin-like growth factor I led to a rise in plasma concentrations which reached a peak at 5.5 h (413.1±28.2 ng/ml, mean±SEM). Mean growth hormone levels between 20.00 and 08.00 hours were significantly reduced after recombinant insulin-like growth factor I (19.4±4.0 compared with 33.6±5.8 mU/l; p=0.01), as were the insulin requirements for euglycaemia (0.25±0.02 compared with 0.31±0.04 mU · kg−1 · min−1; p=0.03). Plasma free insulin levels were lower after recombinant insulin-like growth factor I administration (31.9±2.7 compared with 67.9±16.0 mU/l; p=0.001) but no significant differences in ketone or lactate levels were detected. Recombinant insulin-like growth factor I in a s. c. dose of 40 μg/kg body weight leads to a significant reduction in overnight growth hormone levels and insulin requirements in adolescents with Type 1 diabetes.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; islet-cell antibodies ; insulin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Basal insulin secretion was compared in nine islet-cell antibody positive, non-diabetic first-degree relatives of children with Type 1 (insulin-dependent) diabetes mellitus and nine normal control subjects matched for age, sex and weight. Acute insulin responses to a 25 g intravenous glucose tolerance test were similar in the two groups (243 (198–229) vs 329 (285–380) mU·l−1·10min−1, mean (±SE), p=0.25). Fasting plasma insulin was assayed in venous samples taken at one min intervals for 2 h. Time series analysis was used to demonstrate oscillatory patterns in plasma insulin. Autocorrelation showed that regular oscillatory activity was generally absent in the islet-cell antibody positive group, whereas a regular 13 min cycle was shown in control subjects (p〈 0.0001). Fourier transformation did, however, show a 13 min spectral peak in the islet-cell antibody positive group, consistent with intermittent pulsatility. We conclude that overall oscillatory patters of basal insulin secretion are altered in islet-cell antibody positive subjects even when the acute insulin response is within the normal range.
    Type of Medium: Electronic Resource
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