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  • 1
    ISSN: 1432-1041
    Keywords: Key words Glycaemic control ; Insulin-fixed mixture ; Premixed insulins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Background: Pre-mixed insulins currently represent about 40% of the world market in human insulin. Despite the fact that many patients are being treated with these insulin formulations, there are surprisingly few data about fixed mixtures and comparisons with other administration schedules. The main advantages of using a pre-mixed preparation over a self-mixed insulin are increased accuracy of dosage, efficacy and patient convenience. These benefits may lead to increased compliance resulting in better long-term control of the disease. Insulin mixtures are used by a wide variety of patients with type-1 and type-2 diabetes. Premixed insulins also appear to be useful in elderly and adolescent patients with diabetes, although there are few published data on patients in these groups. Conclusions: It is likely that, in the future, fixed mixtures containing rapid-acting insulin analogues, such as insulin lispro, and possibly newly formulated intermediate-acting insulin analogues, such as neutral protamine lispro, may allow further improvements in both metabolic control and patient convenience.
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  • 2
    ISSN: 1432-1076
    Keywords: Vitamin B12 ; Folates ; Megaloblastic anaemia ; Methylmalonic aciduria ; Homocystinuria ; Anaemia in infancy and childhood ; Cobalamins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This review discusses recent knowledge of the many causes of cobalamin deficiency in infancy and childhood. These causes are classified as (1) inadequate intake, (2) inadequate absorption and (3) inadequate utilisation. It is emphasized that the ‘serum B12’ may be normal in cases of the grossest derangement of B12 metabolism, with extreme functional deficiency of this group of vitamins (the cobalamins). For completeness, causes of folate deficiency and other conditions causing megaloblastosis in children are also briefly outlined.
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  • 3
    ISSN: 1432-5233
    Keywords: Glycerol kinetics ; 13C-glycerol ; 2H-glycerol ; Stable isotope tracers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract For a tracer to be valid it must follow the metabolism of the tracee without distortion. Especially when the tracer contains several deuterium substitutions, the tracer can be altered or degraded differently from the metabolite it is to trace or be subject to distorting isotope effects. To determine whether2H5-glycerol is a valid tracer for following glycerol kinetics,2H5-glycerol and [2-13C] glycerol tracers were infused simultaneously in six healthy postabsorptive adult subjects. After 90 min of tracer infusion, epinephrine was also infused for 60 min to stimulate lipolysis and increase glycerol flux. Glycerol flux increased from 2.2±0.3 to 6.7±0.4 μmol/kg per minute (with the13C tracer) and from 2.2±0.3 to 6.7±0.3 μmol/kg per minute (with the2H tracer) when epinephrine was infused. There was no significant difference in glycerol flux measured with the2H tracer compared to the13C tracer either under basal or a stimulated flux condition. These results indicate that2H5-glycerol is a valid tracer for measuring glycerol metabolism in humans.
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  • 4
    ISSN: 1432-0428
    Keywords: Quantitative morphometry ; amyloid ; diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Quantitative morphometry of the pancreases of five ‘maturity-onset’ diabetic subjects has demonstrated more amyloid in islets of the head, body and tail (where it was found in a mean 29% of the islets occupying a mean 11% islet area) than in islets of the ‘pancreatic-polypeptide-rich’ lobule of the head (where amyloid was found in a mean of 3% of the islets occupying a mean of 0.7% islet area, both p〈 0.005). The nonuniform amyloid distribution may relate to the hormone content of the islet; the head and tail contained significantly more A, B and D-cells than the pancreatic-polypeptide-rich lobule in both non-diabetic subjects (n = 8) and diabetic patients (n = 5; p〈0.005). This result is compatible with the previous suggestion that amyloid may be derived from insulin or its precursors.
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  • 5
    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.
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  • 6
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 7
    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.
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  • 8
    ISSN: 1432-0428
    Keywords: Insulin resistance ; β-cell function ; mathematical model ; glucose infusion ; Type 2 diabetes ; plasma insulin ; plasma glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Continuous infusion of glucose with model assessment (CIGMA) is a new method of assessing glucose tolerance, insulin resistance and β-cell function. It consists of a continuous glucose infusion 5 mg glucose/kg ideal body weight per min for 60 min, with measurement of plasma glucose and insulin concentrations. These are similar to postprandial levels, change slowly, and depend on the dynamic interaction between the insulin produced and its effect on glucose turnover. The concentrations can be interpreted using a mathematical model of glucose and insulin homeostasis to assess insulin resistance and β-cell function. In 23 subjects (12 normal and 11 with Type 2 (non-insulin-dependent diabetes) the insulin resistance measured by CIGMA correlated with that measured independently by euglycaemic clamp (Rs = 0.87, p 〈 0.0001). With normal insulin resistance defined as 1, the median resistance in normal subjects was 1.35 by CIGMA and 1.39 by clamp, and in diabetic patients 4.0 by CIGMA and 3.96 by clamp. In 21 subjects (10 normal and 11 Type 2 diabetic) the β-cell function measured by CIGMA correlated with steady-state plasma insulin levels during hyperglycaemic clamp at 10 mmol/l (Rs=0.64, p 〈 0.002). The CIGMA coefficient of variability was 21% for resistance and 19% for β-cell function. CIGMA is a simple, non-labour-intensive method for assessing insulin resistance and β-cell function in normal and Type 2 diabetic subjects who do not have glycosuria during the test.
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  • 9
    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.
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  • 10
    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.
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