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  • 1
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; retinopathy ; platelet aggregation ; adenosine diphosphate ; prostacyclin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Platelet sensitivity to adenosine diphosphate and prostacyclin in diabetes has been assessed using collision theory and the concept of ‘sticking probability’ (the probability of particle union). Twenty Type 1 (insulin-dependent) diabetic men (10 with no or minimal retinopathy and a matched group of 10 with proliferative retinopathy) and 10 age-matched non-diabetic men were studied. Platelets from the 20 diabetic patients required, on average, 37% less adenosine diphosphate to achieve a sticking probability of 0.5 (ED50) compared with platelets from the non-diabetic subjects (medians 1.50 and 0.95 μmol/l, respectively; p〈0.01). The platelet prostacyclin response was assessed by the dissociation constant (Ki) for inhibition of adenosine diphosphate-induced aggregation. Platelets from the diabetic patients had similar prostacyclin sensitivity to those from the non-diabetic subjects (medians 0.42 and 0.42 respectively). Diabetic patients with and without retinopathy had similar platelet sensitivity to both adenosine diphosphate and prostacyclin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Diabetes ; lipids ; diabetic retinopathy ; cholesterol ; triglycerides ; diabetic nephropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diurnal profiles of total and lipoprotein cholesterol and triglycerides were measured in 11 insulin-dependent diabetic subjects without retinopathy, 10 with background and 10 with proliferative retinopathy. The groups were closely matched for age and duration of diabetes. Total cholesterol levels were higher in patients with proliferative (5.6±0.5 mmol/l) than background (5.1±0.7 mmol/l) or no retinopathy (4.6±0.8 mmol/l, trend test; p 〈 0.003), due to raised levels of low density lipoprotein (LDL) cholesterol (3.8±0.9, 3.2±0.6 and 2.8±0.8 mmol/l respectively; p 〈 0.02). High density lipoprotein (HDL) levels were similar in patients with and without retinopathy and HDL/ LDL ratios were lower with more severe retinopathy (p 〈 0.025). Cholesterol levels were similar in diabetic subjects without retinopathy and in 12 normal subjects. Triglyceride levels were not related to retinopathy and no measure of plasma lipids correlated with HbA1 or 24-h mean plasma glucose. Total and LDL cholesterol were weakly inversely correlated with creatinine clearance but the association with retinopathy was independent of this effect.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 24 (1983), S. 231-237 
    ISSN: 1432-0428
    Keywords: Insulin ; Type 2 diabetes ; oscillations ; pulsations ; man ; vagotomy ; pacemaker ; atropine ; naloxone ; phentolamine ; propranolol ; glucose ; tolbutamide ; sodium salicylate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma insulin and glucose concentrations were examined in man in a basal state from central venous samples taken at 1-min intervals for up to 2.5 h. Normal subjects have insulin oscillations of mean period 14 min (significant autocorrelation, p 〈 0.0001) with changes in concentration of 40% over 7 min. The pulsation frequency was stable through cholinergic, endorphin, α-adrenergic or β-adrenergic blockade, or small pertubations with glucose or insulin. Stimulation of insulin secretion by intravenous glucose, tolbutamide or sodium salicylate increased the amplitude of the insulin oscillations while the frequency remained stable. Patients with a truncal vagotomy or after Whipple's operation had longer-term oscillations of 33 and 37 min periodicity (autocorrelation: p 〈 0.0001), with insulin-associated glucose swings four times larger than those of normal subjects. Type 2 (non-insulin-dependent) diabetic patients had a similarly increased insulin-associated glucose swing of six times that seen in normal subjects. The hypothesis is proposed that the 14-min cycle of insulin production is controlled by a ‘pacemaker’ which assists glucose homeostasis. The longer 33–37-min oscillations, seen in those with denervation, may arise from a limit-cycle of the feedback loop between insulin from the B cells and glucose from the liver. The vagus may provide hierarchical control of insulin release.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Diabetes ; therapy ; diet ; insulin therapy ; sulphonyl-urea ; biguanide ; epidemiology ; body weight ; fasting plasma glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A multi-centre, prospective randomised study of the therapy of maturity-onset diabetes has been started, and we report progress of the first 286 patients with 1-year followup. Newly presenting patients (aged 25–65 years inclusive) were initially treated by diet and divided into three categories. (1) Forty-one patients (14%) were ‘primary diet failure’ in that they continued to have symptoms or their fasting plasma glucose remained 〉15 mmol/l. Their therapy was allocated randomly to insulin, chlorpropamide or glibenclamide, and doses adjusted to try to maintain a fasting plasma glucose 〈6 mmol/l. Insulin produced a similar decrease in fasting plasma glucose to sulphonylurea therapy (median fasting plasma glucose fell from 15.4 to 8.0 mmol/l and from 15.5 to 8.6 mmol/l, respectively). (2) After 3–4 months diet, 161 patients (56%) were asymptomatic but had a fasting plasma glucose 〉6 mmol/l. In the ‘main randomisation’ their therapy was allocated to diet only, or diet plus chlorpropamide, glibenclamide or a basal insulin supplement from ultralente insulin. On diet alone, fasting plasma glucose remained constant over 1-year follow-up (from 7.7 to 7.6 mmol/l), whereas it was reduced significantly by insulin (from 8.0 to 6.4 mmol/l), chlorpropamide (8.6 to 6.1 mmol/l) and glibenclamide (7.8 to 6.5 mmol/l). On diet alone, weight remained unchanged over 1 year but increased significantly on insulin, chlorpropamide or glibenclamide (median change ideal body weight +3.5%, +4% and +4%, respectively). Obese patients (〉20% over ideal weight) did not differ from normal weight diabetic subjects in either fasting plasma glucose or weight changes. Insulin therapy was associated with few hypoglycaemic episodes, with 8% of patients on ultralente insulin alone reporting an episode compared with 7% on chlorpropamide. Fifty-one patients (86%) randomised to insulin remain on it lyear later. (3) After 3–4 months on diet, 84 patients (30%) after dieting had a fasting plasma glucose 〈6 mmol/l. During the following year on diet alone 34 patients were less well controlled with a fasting plasma glucose 〉6 mmol/l and were included in a ‘delayed randomisation’. Thus 83% of all patients entered into the study had their therapy randomised by 1 year. Insulin and sulphonylurea therapy are equally effective in reducing glycaemia, and the study is being extended to determine if either therapy will prevent the complications of diabetes or have untoward long-term side effects.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 571-577 
    ISSN: 1432-0428
    Keywords: Insulinoma ; malignant insulinoma ; proinsulin ; C-peptide ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The value of plasma insulin, human C-peptide and proinsulin estimation in the diagnosis of 15 insulinomas has been investigated. Measurement of plasma proinsulin in an overnight fasting sample diagnosed all the insulinomas studied, irrespective of the plasma glucose. Patients with insulinomas had plasma proinsulin in the range 0.04–4.2 pmol/l and normal values were less than 0.01 pmol/ml. If hypoglycaemia was present, an inappropriately raised plasma immunoreactive insulin (including proinsulin) was diagnostic, but this assay was of little assistance if the plasma glucose was normal. Hypoglycaemia was induced with fish insulin in twelve patients with insulinomas and eight normal subjects. Using an antiserum which did not detect fish insulin, but cross-reacted with human proinsulin, the endogenous immunoreactive insulin was suppressed in the normal subjects, but all insulinoma patients had impaired suppression. Assay of plasma human C-peptide, or of the combined immunoreactive C-peptide and proinsulin, discriminated less well and did not clearly diagnose three insulinomas which secreted proinsulin rather than insulin and C-peptide. Plasma human proinsulin values during induced hypoglycaemia gave excellent discrimination and should detect insulinomas irrespective of their degree of histological differentiation. The assay of plasma human proinsulin allows a suppression test to be performed with hypoglycaemia induced by any type of insulin. A raised plasma proinsulin in proportion to C-peptide suggests an undifferentiated insulinoma, which may be more likely to be malignant.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Untreated maturity-onset diabetes ; plasma cholesterol ; serum triglyceride ; lipoproteins ; ponderal index ; blood glucose ; diet ; sulphonylureas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma cholesterol and serum triglyceride levels and frequency of lipoprotein abnormalities were investigated in 126 untreated maturity-onset diabetics and 126 age- and sexmatched control subjects. Serum triglyceride levels were higher (mean: 1.67 mmol/l) and type IV hyperlipoproteinaemia occurred more frequently (16.7%) in the diabetic group as compared with the controls (1.29 mmol/l and 4.8% respectively). These findings were not explained by an excessive frequency of renal disease, hypertension or drug treatment amongst the diabetics. Normal men showed higher serum triglyceride (mean: 1.36mmol/l) and lower plasma cholesterol (mean: 5.6mmol/l) levels than normal women (1.21 mmol/1 and 6.4mmol/l respectively). No sex difference was seen amongst the diabetics. Triglyceride levels fell after one month of dietary treatment but only remained lowered in diabetics who required sulphonylureas for glycaemic control. After treatment for one year the correlation between serum triglycerides and blood glucose rose from r = 0.15 (NS) before treatment to r=0.43 (p〈0.001). Similarly the correlation between serum triglycerides and ponderal index rose from r=0.19 (NS) to r=0.28 (p〈0.02).
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Insulin therapy ; hypoglycaemia ; plasma insulin ; diabetes control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relative efficacy of two twice-daily insulin regimens using highly purified insulins, once daily Ultratard with twice daily Actrapid (ultralente/soluble) and twice daily Actrapid with twice daily Retard (soluble/isophane), has been studied in 12 diabetics in a cross-over study. Control was optimised as an out-patient, and assessed by in-patient 24 hour profiles. Similar day-time glucose control was achieved, but the mean overnight plasma glucose concentrations were more steady on ultralente/soluble (0100, 0300, 0500, 0700, 0800 h values 5.6, 5.3, 5.8, 7.8, 10.4 mmol/l) than on soluble/isophane (4.3, 3.4, 5.2, 7.5, 12.2 mmol/l). The minimum overnight plasma glucose concentrations were lower (p 〈 0.05) on soluble/isophane (mean 2.8 mmol/l) than on ultralente/soluble (mean 4.8 mmol/l), associated with higher (p 〈 0.05) nocturnal free plasma insulin levels after the evening soluble/isophane injection. The plasma glucose rise between 0700 and 0800 h was greater (p 〈 0.05) on soluble/isophane than on ultralente/soluble. The morning insulin injection should probably be taken immediately on rising, to prevent the pre-breakfast plasma glucose rise. The ultralente/ soluble combination gave similar day-time plasma glucose control to soluble/isophane with less nocturnal hypoglycaemia.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: N-acetyl-β ; D-glucosaminidase ; hyperglycaemia ; glycosylated haemoglobin ; insulin infusion ; diurnal variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma activity of the lysosomal enzyme N-acetyl-β, D-glucosaminidase (NAGase) has been shown to correlate with hyperglycaemia; their temporal relationships have been investigated. In 12 insulin-treated male diabetic patients, NAGase showed a slight diurnal variation with a nadir at 07.00 h (F=9.54, p〈0.001). The mean plasma glucose and NAGase fluctuated similarly (rs=0.88, p〈0.01) but did not correlate within individual patients. Normoglycaemia was induced in eight insulin-treated diabetic patients for 4 days but the mean NAGase did not fall significantly. Glycaemic improvement over 3 months was achieved by dietary therapy in 28 newly-presenting non-insulin-dependent diabetic patients: there were significant falls in mean fasting plasma glucose (mean±SD: 12.8±3.3 to 8.3±3.1 mmol/l; p〈0.001), glycosylated haemoglobin levels (12.4±2.4 to 9.3±2.3%, p〈 0.001) and a corresponding decrease of NAGase (1.5±0.5 to 1.2±0.4 μmol 4-nitrophenyl-N-acetyl-β-D-glucosamide released.h−1.ml−1; p〈0.001). The change in NAGase correlated with the changes in plasma glucose and glycosylated haemoglobin levels (r = 0.61, p〈0.025; r = 0.48, p〈0.05, respectively). Plasma NAGase activity may be influenced by glycaemia in diabetes.
    Type of Medium: Electronic Resource
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  • 9
    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.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; genetics ; liver/islet glucose transporter gene ; restriction fragment length polymorphism ; population association study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The liver/islet glucose transporter (GLUT2) is expressed in the liver and in the Beta cells of pancreatic islets and is a candidate gene for the inherited defect in Type 2 (non-insulin-dependent) diabetes mellitus. A series of restriction fragment length polymorphisms have been identified using a GLUT2 cDNA probe with five restriction enzymes in a British white Caucasian population. Five independent restriction fragment length polymorphisms detected by restriction enzymes EcoRI (two restriction fragment length polymorphisms termed EcoRI-1, EcoRI-2), TaqI (two restriction fragment length polymorphisms termed TaqI-1, TaqI-2), and BclI (BclI-2) were used to construct GLUT2 haplotypes. Significant linkage disequilibrium was observed between four polymorphic sites EcoRI-2, TaqI-1, TaqI-2 and BclI-2 but linkage disequilibrium was not observed with EcoRI-1 polymorphic site and the other four sites. The frequencies of GLUT2 restriction fragment length polymorphisms and haplotypes in 50 Type 2 diabetic subjects and 50 non-diabetic control subjects show no significant differences suggesting that it is unlikely that there is a single major defect of this gene contributing to the inherited susceptibility to Type 2 diabetes in a Caucasian population.
    Type of Medium: Electronic Resource
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