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  • 1
    ISSN: 1432-0428
    Keywords: Glycated haemoglobin ; glucose intolerance ; ambient blood-glucose levels ; dietary carbohydrate ; dietary fibre
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied levels of glycated haemoglobin in a sample of 223 people aged over 40 years without known diabetes mellitus screened in a community study. Each had a glucose tolerance test and glycated haemoglobin measured by four methods — agar gel electrophoresis with and without removal of Schiff base, affinity chromatography and isoelectric focusing. The correlation coefficients between 2 h blood glucose and levels of glycated haemoglobin were between 0.43 and 0.64. This poor correlation was not explained on the basis of assay or biological variability of either 2 h blood glucose or glycated haemoglobin. Multiple regression analysis showed that other assays of glycated haemoglobin contributed to the variance of any single glycated haemoglobin value by 0.1%–52.9% (median 12.8%) compared to the variance of 18.6%–41.4% (median 30.8%) explained by 2 h blood glucose alone, suggesting that in a non-diabetic population, the degree of glucose intolerance may explain only one third of the variance of glycated haemoglobin levels, but other factors operate to produce consistent changes in levels of glycated haemoglobin. Investigation of 42 subjects with consistently high (20 subjects) or low (22 subjects) levels of glycated haemoglobin relative to their 2 h blood glucose level showed no difference in age, gender, body mass index, haemoglobin levels or smoking, although 50% of low glycators had impaired glucose tolerance. Neither ambient bloodglucose levels, as estimated on two five-point blood-glucose profiles, nor dietary intake of carbohydrate, starch, sugars, fibre or alcohol, explained the difference between high and low glycators. The determinants of the consistent interindividual differences in levels of glycated haemoglobin in nondiabetic subjects remain to be determined.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Glycaemic control ; insulin ; sulphonylureas ; insulin resistance ; endothelial dysfunction ; tumour necrosis factor-α ; interleukin-6 ; C-reactive protein.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Improved glycaemic control might reduce both microvascular and macrovascular complications of Type II diabetes (non-insulin-dependent) mellitus. To explore such possible mechanisms, we investigated the effects of intensive treatment on markers of endothelial dysfunction and of acute phase activation, using both sulphonylureas and insulin. Methods. In a randomised cross-over study we gave sulphonylureas or insulin each for a period of 16 weeks to 22 poorly controlled Type II diabetic subjects who were being treated by diet. There was a 4 week washout period between each treatment. Subjects were studied at baseline and at the end of each treatment. Results. Treatment with sulphonylureas and insulin resulted in similar improvements in glycaemic control (glycated haemoglobin, baseline: 11.8 [(SD 2.2)%; after sulphonylureas: 8.6 (1.2)%, p 〈 0.001; after insulin: 8.6 (1.2)%, p 〈 0.001] and in insulin sensitivity {metabolic clearance rate of glucose, baseline: median 1.75 [interquartile (IQ) range 1.41, 2.27] ml · kg–1· min–1; after sulphonylureas: 2.41 (1.82, 3.01) ml · kg–1· min–1, p = 0.001; after insulin: 2.23 (1.92, 2.75) ml · kg–1· min–1, p = 0.027}. There were no significant changes in concentrations of endothelial markers von Willebrand factor, cellular fibronectin, thrombomodulin, tissue plasminogen activator, soluble E-selectin or soluble intercellular adhesion molecule-1 or in urinary albumin excretion rate after either treatment period. Concentrations of C-reactive protein were not significantly influenced by sulphonylureas but fell after insulin [baseline: median 4.50 (IQ range 1.37, 6.44) μg · ml–1; sulphonylureas: 2.69 (0.88, 9.65) μg · ml–1 (p = 0.53); insulin: 2.07 (1.16, 5.24) μg · ml–1 (p = 0.017)]. There were, however, no significant effects of either treatment on circulating concentrations of fibrinogen (p = 0.28–0.34) or of the proinflammatory cytokines interleukin-6 or tumour necrosis factor-α (p = 0.65–0.79). Conclusion/interpretation. Markers of endothelial dysfunction and concentrations of proinflammatory cytokines in Type II diabetes are not influenced by improved glycaemic control over 16 weeks. Improved metabolic control with insulin could, however, be associated with reduced concentrations of the acute phase marker C-reactive protein. [Diabetologia (2000) 43: 1099–1106]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: 32–33 splet-proinsulin ; Total cholesterol ; high density lipoprotein cholisterol ; plasminogen activator inhibitor ; Blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Standard radioimmunoassay for insulin may substantially overestimate levels of insulin because of cross-reaction with other insulin-like molecules. We have measured concentrations of insulin, intact proinsulin and 32–33 split proinsulin using two-site monoclonal antibody based immunoradiometric assays, and of insulin by a standard radioimmunoassay (“immunoreactive insulin”) in 51 Type 2 (noninsulin-dependent) diabetic subjects in the fasting state. The relationships of these concentrations were sought with those of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, plasminogen activator inhibitor, blood pressure, and indices of body fat distribution. Significant relationships were apparent between concentrations of “immunoreactive insulin” as measured by standard radioimmunoassay and triglyceride (r s=0.42, p〈0.001), total cholesterol (r s=0.25, p=0.038), high density lipoprotein cholesterol (r s=−0.30, p=0.018) and body mass index (r s=0.30, p=0.017), but only the relationships with triglyceride (r s=0.36, p=0.006) and body mass index (r s=0.26, p=0.034) remained significant when concentrations of immunoradiometrically measured insulin were employed. Concentrations of 32—33 split proinsulin, which comprises the major insulin-like molecule in these subjects, correlated positively with triglyceride (r s=0.33, p=0.009), total cholesterol (r s=0.23, p=0.050), and plasminogen activator inhibitor (r s=0.26, p=0.049), and negatively with high density lipoprotein cholesterol (r s=−0.29, p=0.021). Concentrations of “immunoreactive insulin” and immunoradiometric assay insulin showed significant positive correlaion with both systolic (r s=0.24, p=0.044 and r s=0.29, p=0.020 respectively), and diastolic blood pressure (r s=0.48, p〈0.001 and n=0.42, p=0.001 respectively), while those of intact proinsulin and 32–33 split proinsulin correlated only with diastolic blood pressure (r s=0.33, p=0.009 and r s=0.31, p=0.014 respectively). Using multiple regression analysis, and including age, sex, race and body mass index in the analyses, concentrations of intact proinsulin and 32–33 split proinsulin, but not immunoradiometric assay insulin, were significantly related to diastolic blood pressure. When all three molecules were incorporated into a single model, only 32–33 split proinsulin was related to diastolic blood pressure (F-change=6.91, [5,43 degrees of freedom]; p=0.012). Thus, high concentrations of insulin-like molecules are associated with changes in recognised cardiovascular risk factor in patients with Type 2 (non-insulin-dependent) diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Key words Proinsulin-like molecules ; cardiovascular risk factors ; insulin ; insulin resistance ; beta-cell function.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Elevated concentrations of proinsulin-like molecules, other than insulin, may be associated with abnormalities of cardiovascular risk factors, promoting atherogenesis and thrombosis. Using specific assays we examined the relationship of levels of insulin, intact proinsulin and des-31,32 proinsulin to blood pressure, lipids, fibrinogen, factor VII and albumin excretion rate in 270 europids with normal glucose tolerance. After correcting for age and body mass index, fasting and 2-h insulin concentrations were significantly associated with those of total and LDL-cholesterol (r = 0.18–0.22), HDL-cholesterol (both r = – 0.20) and triglycerides (r = 0.21 and 0.18), but not with blood pressure. Concentrations of intact and des-31,32 proinsulin showed significant associations with those of total and LDL-cholesterol (r = 0.20–0.23), HDL-cholesterol (r = –0.31 and –0.32) and triglycerides (r = 0.22 and 0.26). Fasting insulin and intact proinsulin concentrations were significantly associated with fibrinogen (r = 0.15 and 0.18). Concentrations of proinsulin-like molecules comprised less than 10 % of all insulin-like molecules, and so were calculated not to influence previously described relationships between insulin concentrations and cardiovascular risk factors measured using non-specific assays. In multiple regression analyses des-31,32 proinsulin concentration was more strongly associated with those of HDL-cholesterol (negatively), LDL-cholesterol and triglycerides than fasting insulin concentrations, while intact proinsulin replaced insulin concentrations in their relationships with fibrinogen. Our results show correlations between dyslipidaemia and proinsulin-like molecules at concentrations at which biological, insulin-like, activity appears unlikely. We also show relationships between LDL-cholesterol and fibrinogen and the proinsulin-like molecules. These results suggest that a causal relationship mediated by hyperinsulinaemia and insulin resistance is unlikely. [Diabetologia (1995) 38: 1110–1116]
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  • 5
    ISSN: 1432-0428
    Keywords: Key words Non-insulin-dependent diabetes ; microalbuminuria ; hypertension ; sodium-lithium countertransport.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased erythrocyte sodium-lithium countertransport rate is found in non-diabetic subjects with essential hypertension, and in insulin-dependent diabetic subjects with nephropathy. However, relationships between these variables in non-insulin-dependent diabetic subjects are ill-defined. In order to characterise the relationships between blood pressure, urinary albumin excretion, and erythrocyte sodium-lithium countertransport, 66 subjects with non-insulin-dependent diabetes were studied. Urinary albumin excretion rate correlated with mean 24-h ambulatory systolic blood pressure (r = 0.57; p 〈 0.001), but not with sodium-lithium countertransport (r = 0.06; p = 0.31). No significant relationship was observed between 24-h systolic blood pressure and erythrocyte sodium-lithium countertransport (r = 0.16; p = 0.17). The principal differences between microalbuminuric and normoalbuminuric subjects (albumin excretion rate 〉 15 μg · min−1 [n = 20], and 〈 15 μg · min−1, [n = 46]) were: higher 24-h systolic blood pressure (145.9 [16.8] mm Hg vs 131.9 [16.8] mm Hg; p = 0.006), nocturnal heart rate (72.4 [8.9] vs 67.4 [8.9] beats · min−1; p = 0.042), and HbA1 (11.3 [1.5] % vs 10.1 [2.0] %; p = 0.028), and a longer median duration of diabetes (10.0 vs 5.0 years; p = 0.02). In contrast, there was no significant difference in sodium-lithium countertransport rate between microalbuminuric (0.41 [0.18] mmol · l−1· h−1) and normoalbuminuric subjects (0.39 [0.15] mmol · l−1· h−1; p = 0.687). In multiple regression analysis controlling for race, age, body mass index and HbA1, the significant determinants of albumin excretion rate were 24-h systolic blood pressure (B [regression coefficient] = 0.029, SE[B] [standard error of B] = 0.009, t = 2.95, p = 0.005), duration of diabetes (B = 0.430, SE[B] = 0.169, t = 2.54, p = 0.016) and male gender (B = −1.170, SE[B] = 0.457, t = −2.56, p = 0.015). In conclusion, albumin excretion rates in non-insulin-dependent diabetic subjects are linked to hypertension and glycaemic exposure, but show no relationship to erythrocyte sodium-lithium countertransport. [Diabetologia (1995) 38: 356–362]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Left ventricular hypertrophy ; diabetes mellitus ; sodium-lithium countertransport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The determinants of left ventricular mass in normal control subjects and subjects with non-insulindependent diabetes (NIDDM) are ill-defined. We therefore recorded M-mode and pulsed Doppler echocardiograms and 24-h ambulatory blood pressure in 57 normotensive subjects, 34 with NIDDM and 23 matched non-diabetic control subjects. Measurements of erythrocyte sodium-lithium countertransport, plasma angiotensin II, plasma and platelet catecholamines and fasting plasma insulin were also made. Six control subjects (26%) and 15 diabetic subjects (44%) had some degree of left ventricular hypertrophy. Subjects with left ventricular hypertrophy (n=21) had an elevated mean rate of sodium-lithium countertransport (0.40±0.13 vs 0.31±0.09 mmol·l−1 ·h−1; p〈0.01), parallel differences being observed in both the diabetic and control groups. Twelve of the subjects with left ventricular hypertrophy (57%) had elevated rates of sodium-lithium counter-transport compared to only seven (19%) of those without (p〈0.05). There was no consistent difference between those with and without left ventricular hypertrophy in any other clinical or biochemical variable. Multivariate analysis, with the presence or absence of left ventricular hypertrophy as the dependent variable, demonstrated that the maximal rate of sodium-lithium countertransport was the only variable that independently contributed to left ventricular hypertrophy (partial r=0.35; F 1.55=7.74; p = 0.007). This study demonstrates for the first time an association between left ventricular hypertrophy and erythrocyte membrane cation transport that is independent of hypertension, is present in both diabetic and non-diabetic groups, and may represent a link between elevated rates of membrane sodium transport and cardiovascular risk.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes ; micro-albuminuria ; hypertension ; sodium-lithium countertransport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased erythrocyte sodium-lithium countertransport rate is found in non-diabetic subjects with essential hypertension, and in insulin-dependent diabetic subjects with nephropathy. However, relationships between these variables in non-insulin-dependent diabetic subjects are ill-defined. In order to characterise the relationships between blood pressure, urinary albumin excretion, and erythrocyte sodium-lithium countertransport, 66 subjects with non-insulin-dependent diabetes were studied. Urinary albumin excretion rate correlated with mean 24-h ambulatory systolic blood pressure (r=0.57; p〈0.001), but not with sodium-lithium countertransport (r=0.06; p=0.31). No significant relationship was observed between 24-h systolic blood pressure and erythrocyte sodium-lithium countertransport (r = 0.16; p=0.17). The principal differences between microalbuminuric and normoalbuminuric subjects (albumin excretion rate 〉15 Μg·min−1 [n=20], and 〈15 Μg·min−1, [n=46]) were: higher 24-h systolic blood pressure (145.9 [16.8] mm Hg vs 131.9 [16.8] mm Hg; p=0.006), nocturnal heart rate (72.4 [8.9] vs 67.4 [8.9] beats·min−1; p=0.042), and HbA1 (11.3 [1.5]% vs 10.1 [2.0]%; p=0.028), and a longer median duration of diabetes (10.0 vs 5.0 years; p = 0.02). In contrast, there was no significant difference in sodium-lithium countertransport rate between microalbuminuric (0.41 [0.18] mmol·l−1·h−1) and normoalbuminuric subjects (0.39 [0.15] mmol·l−1· h−1; p=0.687). In multiple regression analysis controlling for race, age, body mass index and HbA1, the significant determinants of albumin excretion rate were 24-h systolic blood pressure (B [regression coefficient]=0.029, SE[B] [standard error of B]=0.009, t=2.95, p=0.005), duration of diabetes (B=0.430, SE[B]=0.169, t=2.54, p=0.016) and male gender (B=−1.170, SE[B]=0.457, t=−2.56, p=0.015). In conclusion, albumin excretion rates in non-insulin-dependent diabetic subjects are linked to hypertension and glycaemic exposure, but show no relationship to erythrocyte sodium-lithium countertransport.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Key words Left ventricular hypertrophy ; diabetes mellitus ; sodium-lithium countertransport.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The determinants of left ventricular mass in normal control subjects and subjects with non-insulin-dependent diabetes (NIDDM) are ill-defined. We therefore recorded M-mode and pulsed Doppler echocardiograms and 24-h ambulatory blood pressure in 57 normotensive subjects, 34 with NIDDM and 23 matched non-diabetic control subjects. Measurements of erythrocyte sodium-lithium countertransport, plasma angiotensin II, plasma and platelet catecholamines and fasting plasma insulin were also made. Six control subjects (26 %) and 15 diabetic subjects (44 %) had some degree of left ventricular hypertrophy. Subjects with left ventricular hypertrophy (n = 21) had an elevated mean rate of sodium-lithium countertransport (0.40 ± 0.13 vs 0.31 ± 0.09 mmol · l− 1· h− 1; p 〈 0.01), parallel differences being observed in both the diabetic and control groups. Twelve of the subjects with left ventricular hypertrophy (57 %) had elevated rates of sodium-lithium countertransport compared to only seven (19 %) of those without (p 〈 0.05). There was no consistent difference between those with and without left ventricular hypertrophy in any other clinical or biochemical variable. Multivariate analysis, with the presence or absence of left ventricular hypertrophy as the dependent variable, demonstrated that the maximal rate of sodium-lithium countertransport was the only variable that independently contributed to left ventricular hypertrophy (partial r = 0.35; F 1.55 = 7.74; p = 0.007). This study demonstrates for the first time an association between left ventricular hypertrophy and erythrocyte membrane cation transport that is independent of hypertension, is present in both diabetic and non-diabetic groups, and may represent a link between elevated rates of membrane sodium transport and cardiovascular risk. [Diabetologia (1995) 37: 454–460]
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Proinsulin-like molecules ; cardiovascular risk factors ; insulin ; insulin resistance ; beta-cell function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Elevated concentrations of proinsulin-like molecules, other than insulin, may be associated with abnormalities of cardiovascular risk factors, promoting atherogenesis and thrombosis. Using specific assays we examined the relationship of levels of insulin, intact proinsulin and des-31,32 proinsulin to blood pressure, lipids, fibrinogen, factor VII and albumin excretion rate in 270 europids with normal glucose tolerance. After correcting for age and body mass index, fasting and 2-h insulin concentrations were significantly associated with those of total and LDL-cholesterol (r=0.18–0.22), HDL-cholesterol (both r=−0.20) and triglycerides (r=0.21 and 0.18), but not with blood pressure. Concentrations of intact and des-31,32 proinsulin showed significant associations with those of total and LDL-cholesterol (r=0.20–0.23), HDL-cholesterol (r=−0.31 and −0.32) and triglycerides (r=0.22 and 0.26). Fasting insulin and intact proinsulin concentrations were significantly associated with fibrinogen (r=0.15 and 0.18). Concentrations of proinsulin-like molecules comprised less than 10% of all insulin-like molecules, and so were calculated not to influence previously described relationships between insulin concentrations and cardiovascular risk factors measured using non-specific assays. In multiple regression analyses des-31,32 proinsulin concentration was more strongly associated with those of HDL-cholesterol (negatively), LDL-cholesterol and triglycerides than fasting insulin concentrations, while intact proinsulin replaced insulin concentrations in their relationships with fibrinogen. Our results show correlations between dyslipidaemia and proinsulin-like molecules at concentrations at which biological, insulin-like, activity appears unlikely. We also show relationships between LDL-cholesterol and fibrinogen and the proinsulin-like molecules. These results suggest that a causal relationship mediated by hyperinsulinaemia and insulin resistance is unlikely.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Keywords Plasminogen activator inhibitor-1 ; fibrinolysis ; Pima Indians ; polymorphism ; genetic ; diabetes mellitus ; non-insulin-dependent.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Elevated plasminogen activator inhibitor-1 may contribute to vascular disease in diabetes mellitus. Pima Indians have a low incidence of cardiovascular disease despite having a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM) which in this population is not associated with elevated plasminogen activator inhibitor-1 activity. In Caucasians an insertion/deletion (4G/5G) polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene that has been related to activity levels of its protein in plasma differentially binds repressor and enhancer elements. In 265 Pima Indians (133 diabetic, 132 non-diabetic, 129 male, 136 female, mean age 46.6, range 34–68 years) the promoter genotype frequencies were 23.0 % for 4G/4G, 49.8 % for 4G/5G and 27.2 % for 5G/5G compared to 35.4 %, 50.8 % and 13.8 % respectively (χ2 = 15.3, 2 df, p 〈 0.0005) previously reported in Caucasians with NIDDM. The mean plasma activity levels in the three genotypes in the Pima Indians were 18.2, 19.1 and 18.1 U/ml, respectively. Plasminogen activator inhibitor-1 activities correlated with plasma insulin (r = 0.38, p 〈 0.0001), body mass index (r = 0.24, p 〈 0.0001), and with triglyceride level (r = 0.12, p = 0.054) but there was no relationship between promoter genotype and activity. A steeper regression slope between plasminogen activator inhibitor-1 activity and triglycerides has been observed in Caucasians with the 4G/4G genotype as compared to Caucasians with the other genotypes. This was not found in the Pima population which may indicate a functional difference in this gene associated with reduced cardiovascular risk and may be involved in the lack of association of plasminogen activator inhibitor-1 levels with NIDDM in Pima Indians. [Diabetologia (1996) 39: 1512–1518]
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