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 micrograms.min-1 [n = 20], and < 15 micrograms.min-1, [n = 46]) were: higher 24-h systolic blood pressure (145.9 [16.8] mmHg vs 131.9 [16.8] mmHg; 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).(ABSTRACT TRUNCATED AT 250 WORDS)

Age of Onset↗

PubMed1995

Association between left ventricular hypertrophy and erythrocyte sodium-lithium exchange in normotensive subjects with and without NIDDM.

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 counter-transport, 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; F1.55 = 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.

Adult↗

PubMed1995

The contribution of proinsulin and des-31,32 proinsulin to the hyperinsulinemia of diabetic and nondiabetic cirrhotic patients.

We used specific, monoclonal antibody-based, two-site immunoradiometric assays to test the hypothesis that serum levels of proinsulin and des-31,32 proinsulin would be increased in cirrhosis, particularly in those with overt diabetes. A 75-g oral glucose tolerance test was performed after an overnight fast in eight cirrhotic patients with diabetes (fasting blood glucose, 7.8 +/- 2.2 [SE] mmol/L), seven nondiabetic cirrhotic patients, and eight normal control subjects. Fasting serum immunoreactive insulin levels were approximately six times higher in cirrhotics than in controls, but were not different between diabetic and nondiabetic cirrhotic patients. After oral glucose, the incremental area under the serum insulin concentration curve was 3,475 +/- 1,009 pmol.L-1.h in nondiabetic cirrhotic patients, significantly higher than in controls (761 +/- 48, P < .001) or diabetic cirrhotic patients (881 +/- 186, P < .05). Fasting serum proinsulin levels in diabetic cirrhotic patients (24.0 +/- 5.7 pmol/L) were higher than in controls (2.3 +/- .05, P < .001) or nondiabetic cirrhotic patients (4.4 +/- 0.8, P < .005). Fasting serum levels of des-31,32 proinsulin were also much higher in diabetic cirrhotic patients than in nondiabetic cirrhotic patients or controls (P < .02 and P < .005, respectively). Fasting proinsulin plus des-31,32 proinsulin constituted 12.5% +/- 1.4% of serum immunoreactive insulin in diabetic cirrhotics, higher than in nondiabetic cirrhotics (3.7% +/- 0.5%, P < .001) and normal controls (7.8% +/- 1.5%, P = .035).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Coronary heart disease in diabetes mellitus: three new risk factors and a unifying hypothesis.

The standard risk factors--dyslipidaemia, hypertension and smoking--provide little help in explaining the raised cardiovascular risk in diabetes. It can be calculated that intervening for disturbances of these risk factors could do little to rectify the loss of life expectancy of around 10 years for a middle-aged diabetic man. Three new risk factors are discussed, which together may contribute to some of the excess cardiovascular risk in diabetes. Plasminogen activator inhibitor is an inhibitor of fibrinolysis which is elevated in concentration in diabetic subjects, and may increase both the incidence of thrombotic events and the risk of reinfarction after the initial infarct. Recent work also suggests that high activity of this substance may impair pharmacological fibrinolysis. Proinsulin-like molecules are elevated in concentration in diabetic patients and correlate with levels of a number of other risk factors. Whilst these correlations may represent cause and effect for plasminogen activator inhibitor, there is no evidence that changes in levels of proinsulin-like molecules influence levels of other risk factors. Microalbuminuria provides a powerful indicator of cardiovascular risk in both diabetic and non-diabetic subjects, but whilst the mechanisms for this association are unclear, they are again unlikely to be mediated through changes in levels of standard risk factors. Recent observations of an association between short stature and microalbuminuria suggest that intrauterine or early infant nutrition may represent a common antecedent, these having also been shown to predict both components of the insulin resistance syndrome and cardiovascular disease in adult life.

Albuminuria↗

PubMed1995

Longitudinal study of associations of microalbuminuria with the insulin resistance syndrome and sodium-lithium countertransport in nondiabetic subjects.

Microalbuminuria in diabetic patients is associated with ischemic heart disease and insulin resistance. We previously found a 9% prevalence of microalbuminuria in a nondiabetic population that we have reassessed, investigating associations of microalbuminuria with hypertension, dyslipidemia, hyperinsulinemia, and sodium-lithium countertransport. Of 125 subjects reexamined, 42 had been microalbuminuric 3 years previously. Twelve of these (29%) were microalbuminuric on at least one sample at follow-up, and 30 (76%) were normoalbuminuric on two. Of the 79 previously normoalbuminuric subjects, 12 (15%) became microalbuminuric on one sample, while 67 (85%) remained normoalbuminuric. Subjects who were microalbuminuric at both screening and recall were older (mean +/- SD, 65.9 +/- 11 versus 59.1 +/- 10.2 years, P = .04), with a higher waist-to-hip ratio (0.93 +/- 0.09 versus 0.86 +/- 0.08, P = .008) and at recall, on univariate analysis, had higher specific insulin (44.2 [range, 16.9 to 157.0] versus 28.4 [7.4 to 129.0] pmol/L, P = .005), intact proinsulin (5.1 [1.5 to 11.0] versus 3.0 [0.8 to 14.6] pmol/L, P = .003), and des-31,32-proinsulin (5.0 [0.5 to 9.8] versus 1.0 [0.5 to 12.2] pmol/L, P = .004) concentrations. There was also a significant difference in des-31,32-proinsulin concentration, after adjustment for covariates (P = .013), between subjects classified either as microalbuminuric or as normoalbuminuric at screening. There was no difference in body mass index; fasting blood glucose; systolic or diastolic blood pressure; total, HDL, or LDL cholesterol; triglycerides; plasminogen activator inhibitor-1; or sodium-lithium countertransport activity between consistently normoalbuminuric and persistently microalbuminuric subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

The contribution of the sympathoadrenomedullary system to the etiology of essential hypertension: a study using plasma and platelet catecholamine concentrations.

Platelets take up and store noradrenaline and adrenaline in proportion to plasma concentrations and may, therefore, provide an integrated index of sympathoadrenomedullary arousal. Plasma and platelet catecholamine concentrations were measured in 290 European and 155 Asian subjects, and were related to blood pressure, insulin levels, and social class. Plasma noradrenaline concentrations correlated with systolic and diastolic blood pressure in both ethnic groups (r = 0.20-0.30), and these levels were significantly elevated in hypertensive subjects (P < 0.003). In Europeans, but not in Asians, these relationships remained significant after adjusting for age and gender, and were independent of the relationship between insulin and blood pressure. There were much weaker relationships between platelet catecholamine concentrations and blood pressure, which were dependent on age and gender as covariates. In neither ethnic group was there any relationship of either plasma or platelet catecholamine concentrations with insulin concentrations, body mass index, or glucose intolerance. European subjects in manual occupations had significantly higher concentrations of plasma noradrenaline than those with nonmanual occupations. The findings suggest a significant role for the sympathetic nervous system in the determination of blood pressure, but do not provide evidence for a connection between hyperinsulinemia and sympathetic nervous system activity. The role of platelet catecholamines as an epidemiological marker of stress has not been supported.

Adolescent↗

PubMed1995

Determinants of plasminogen activator inhibitor 1 activity in treated NIDDM and its relation to a polymorphism in the plasminogen activator inhibitor 1 gene.

Plasminogen activator inhibitor 1 (PAI-1) activity is increased in patients with non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to their excess risk of cardiovascular disease. We examined the determinants of PAI-1 activity in 146 NIDDM subjects by using specific assays of insulin and intact and des-31,32-proinsulin and measures of insulin resistance, relating these measurements to serum lipids, hypoglycemic therapy, and a common 4G/5G polymorphism in the promoter region of the PAI-1 gene. Subjects were treated with insulin, sulfonylurea, sulfonylurea plus metformin, metformin, and diet alone. In the whole group, PAI-1 activity correlated significantly with serum triglycerides (r = 0.39, P < 0.001), specific insulin (r = 0.29, P < 0.001), intact proinsulin (r = 0.24, P = 0.004), and des-31,32-proinsulin (r = 0.30, P < 0.001) and in subjects not on insulin (n = 110), with insulin sensitivity (r = -0.42, P < 0.001). There was a significant difference in PAI-1 activity among the three genotypic groups (P = 0.016); subjects with the genotype 4G/4G had PAI-1 levels one-third higher than those with the 5G/5G genotype. In the 4G/4G group, PAI-1 activity correlated significantly with triglyceride levels (r = 0.65, P < 0.0001). There was no significant difference in PAI-1 activity in the different treatment groups despite a significant difference in concentrations of intact and des-31,32-proinsulin. In a multiple regression model, insulin sensitivity and the interaction between PAI-1 4G/5G genotype and triglyceride were the strongest determinants of PAI-1 activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Determinants of plasminogen activator inhibitor-1 activity in survivors of myocardial infarction.

A significant relationship has been described between plasminogen activator inhibitor-1 (PAI-1) and plasma insulin concentrations. However, most radioimmunoassays (RIA) substantially overestimate plasma insulin concentrations because of cross reaction with proinsulin-like molecules and it has been proposed that proinsulin-like molecules may be important determinants of PAI-1 activity. We measured fasting plasma immunoreactive insulin by conventional RIA, fasting plasma insulin (EIMA) by specific two site immunoenzymometric assay, and intact proinsulin and des-31,32-proinsulin by two site immunoradiometric assay (IRMA) in 74 (50 nondiabetic and 24 diabetic) subjects who had survived a myocardial infarction between 6 and 24 months previously. In univariate analysis, PAI-1 activity correlated with serum triglycerides (rs = 0.43; p < 0.0001), insulin sensitivity (rs = -0.30; p = 0.004), and immunoreactive insulin (rs = 0.45; p < 0.0001). However, the relationship between PAI-1 activity and plasma specific insulin (IEMA) was weaker (rs = 0.24; p = 0.019) than those with intact proinsulin (rs = 0.53; p < 0.0001) and des-31,32-proinsulin (rs = 0.54; p < 0.0001) despite the low concentrations of these proinsulin-like molecules. In multiple regression analysis, only des-31,32-proinsulin (p = 0.001) and serum triglycerides (p = 0.013) were significant determinants of PAI-1 activity. In conclusion, these results suggest that proinsulin-like molecules and serum triglycerides are important determinants of PAI-1 activity in survivors of myocardial infarction.

Aged↗

PubMed1994

Insulin resistance and impaired glucose tolerance.

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Adolescent↗

PubMed1992

Developing a district diabetic register.

OBJECTIVES: To compile a district wide diabetic register of all diabetic patients registered with general practitioners in the catchment area of a single district general hospital and to compare different approaches to identifying patients. DESIGN: Information for a register was obtained from general practitioners' practice registers, the Prescription Pricing Authority, and hospital diabetic clinic records. SETTING: Catchment area of an inner London district general hospital with a large diabetic clinic. SUBJECTS: All patients with a diagnosis of diabetes resident in or attending general practitioners or hospital clinics in the district or its catchment area. MAIN OUTCOME MEASURES: Prevalence of diabetes, population of patients elicited by different approaches, proportion attending the local district general hospital, cost of using prescription returns for identifying diabetic patients. RESULTS: 4674 patients with diabetes were identified from all sources of information, which corresponds to a mean of 22.4 patients per general practitioner and the prevalence of known diabetes of 1.17%. 39.4% of patients identified had Prescription Pricing Authority returns and 42.8% of patients appeared on practices' diabetic registers. Only 56.5% of patients identified attended the district general hospital. For practices where all sources of information were available, practice registers included 60.4% of all patients, and prescription returns and the clinic register identified 64.9% and 40.6% respectively. The cost of using prescription returns to identify patients not detected in other ways was 6.37 pounds per patient. CONCLUSION: The task of developing district diabetic registers may prove, even in one cross sectional attempt, a major task in many inner city health districts.

Catchment Area, Health↗

PubMed1992

London's health care.

Explore the source record for details and available documents.

Aged↗

PubMed1992

Glucose and insulin infusions during labour.

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Delivery, Obstetric↗

PubMed1992

An algorithm for tight glycaemic control in diabetic infarct survivors.

An algorithm has been developed to provide predictable control of blood glucose for 48 h following acute myocardial infarction. In 29 diabetic patients intravenous infusion of soluble insulin was started upon admission to hospital and the rate adjusted hourly on the basis of bedside capillary glucose estimations. Insulin infusion rates related to glycaemia were higher in obese patients and those with severe cardiac failure. For all patients mean admission glucose levels were reduced from 18.3 +/- 5.9 mmol l-1 to 9.1 +/- 3.3 mmol l-1 at 4 h and to 8.8 +/- 2.5 mmol l-1 at 6 h. Mean glucose concentrations for 48 h after admission were 8.2 +/- 1.3 mmol l-1 for all patients. Admission glucose levels were slightly higher in patients with severe, compared to those without or mild, cardiac failure (P less than 0.1), but levels over the following 48 h were similar. Doubling insulin infusion rates before meals did not achieve tighter glycaemic control. Hypoglycaemia (glucose less than 3 mmol l-1) occurred on 11 occasions in six patients; only two episodes were symptomatic and only two episodes occurred when the insulin rates were doubled before meals. This algorithm produced tighter glycaemic control than previously published protocols, particularly in patients with severe cardiac failure. Hypoglycaemia is uncommon and the algorithm easy to administer by nursing staff.

Algorithms↗