Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care.

Diabetes is considered the commonest cause of end-stage renal disease. The increasing incidence of obesity and an ageing population, together, will lead to a greater number of people with diabetes associated with chronic kidney disease that could either be secondary to diabetic nephropathy or of different aetiology. Ageing and obesity influence approaches to the management of diabetes and accurate assessment of kidney disease. People with diabetes and chronic kidney disease consume a disproportionate component of expenditure on medical care. Guidelines on managing diabetes and kidney disease do not recognize the complex multi-morbid nature of the process. In addition to managing glycaemia and monitoring renal function, the assessment and management of cardiovascular disease risk factors and cardiovascular disease itself need to be factored into care. People with diabetes and diabetic nephropathy are more vulnerable to retinopathy and foot complications requiring coordinated care. People with diabetes and chronic kidney disease are more prone to anaemia and metabolic bone disease than those without diabetes at similar stages of chronic kidney disease, further increasing their vulnerability to acute complications from cardiovascular disease, foot emergencies and fractures. People with diabetes and chronic kidney disease are also more prone to hospitalization with infections and acute kidney injury. Given the 30-40% prevalence of kidney disease amongst people with diabetes, potentially >2% of the adult population would fit into this category, making it vital that new surveillance models of supported care are provided for those living with diabetes and kidney disease and for primary care teams who manage the vast majority of such people.

A national survey of the current state of screening services for diabetic retinopathy: ABCD-diabetes UK survey of specialist diabetes services 2006.

The main aims were to ascertain the progress made in the implementation of retinal screening services and to explore any barriers or difficulties faced by the programmes. The survey focused on all the essential elements for retinal screening, including assessment and treatment of screen-positive cases. Eighty-five per cent of screening programmes have a coordinated screening service and 73% of these felt that they have made significant progress. Eighty-five per cent of screening units use 'call and recall' for appointments and 73.5% of programmes follow the National Screening Committee (NSC) guidance. Although many units worked closely with ophthalmology, further assessment and management of screen-positive patients was a cause for concern. The fast-track referral system, to ensure timely and appropriate care, has been difficult to engineer by several programmes. This is demonstrated by 48% of programmes having waiting lists for patients identified as needing further assessment and treatment for retinopathy. Ophthalmology service for people with diabetic retinopathy was provided by a dedicated ophthalmologist in 89.4% of the programmes. Sixty-six per cent of the programmes reported inadequate resources to sustain a high-quality service, while 26% highlighted the lack of infrastructure and 49% lacked information technology (IT) support. In conclusion, progress has been made towards establishing a national screening programme for diabetic retinopathy by individual screening units, with a number of programmes providing a structured retinal screening service. However, programmes face difficulties with resource allocation and compliance with Quality Assurance (QA) standards, especially those which apply to ophthalmology and IT support. Screening programmes need to be resourced adequately to ensure comprehensive coverage and compliance with QA.

Association of British Clinical Diabetologists (ABCD) and Diabetes-UK survey of specialist diabetes services in the UK, 2006. 1. The consultant physician perspective.

AIMS: To identify the views and working practices of consultant diabetologists in the UK in 2006-2007, the current provision of specialist services, and to examine changes since 2000. METHODS: All 592 UK consultant diabetologists were invited to participate in an on-line survey. Quantitative and qualitative analyses of responses were undertaken. A composite 'well-resourced service score' was calculated. In addition to an analysis of all respondents, a sub-analysis was undertaken, comparing localities represented both in 2006/2007 and in 2000. RESULTS: In 2006/2007, a 49% response rate was achieved, representing 50% of acute National Health Service Trusts. Staffing levels had improved, but remained below recommendations made in 2000. Ten percent of specialist services were still provided by single-handed consultants, especially in Northern Ireland (in 50% of responses, P = 0.001 vs. other nations). Antenatal, joint adult-paediatric and ophthalmology sub-specialist diabetes services and availability of biochemical tests had improved since 2000, but access to psychology services had declined. Almost 90% of consultants had no clinical engagement in providing community diabetes services. The 'well-resourced service score' had not improved since 2000. There was continued evidence of disparity in resources between the nations (lowest in Wales and Northern Ireland, P = 0.007), between regions in England (lowest in the East Midlands and the Eastern regions, P = 0.028), and in centres with a single-handed consultant service (P = 0.001). Job satisfaction correlated with well-resourced service score (P = 0.001). The main concerns and threats to specialist services were deficiencies in psychology access, inadequate staffing, lack of progress in commissioning, and the detrimental impact of central policy on specialist services. CONCLUSIONS: There are continued disparities in specialist service provision. Without effective commissioning and adequate specialist team staffing, integrated diabetes care will remain unattainable in many regions, regardless of reconfigurations and alternative service models.

Relative clinical usefulness of glycosylated serum albumin and fructosamine during short-term changes in glycemic control in IDDM.

Serial changes in glycosylated blood proteins and direct measures of glycemia were studied in 100 subjects with insulin-dependent diabetes mellitus (IDDM) over a 6-wk period while attempts were made to improve glycemic control. All measures of glycemic control improved significantly (P less than .001). Mean +/- SE glycosylated hemoglobin (HbA1) fell from 9.1 +/- 0.2 to 8.0 +/- 0.1%, glycosylated serum albumin (GSA) from 9.8 +/- 0.4 to 7.3 +/- 0.3%, and fructosamine from 3.92 +/- 0.08 to 3.42 +/- 0.07 mM. Fasting blood glucose levels fell from 11.1 +/- 0.6 to 8.1 +/- 0.7 mM mean blood glucose levels from 12.5 +/- 0.3 to 8.8 +/- 0.03 mM, and the M value from 118 +/- 7 to 40 +/- 3 U. Mean percentage changes in direct measures of glycemia (32-66%) and GSA (29%) were greater than for fructosamine (11%) or HbA, (12%) levels (P less than .001). Furthermore, the correlation between the change in GSA and changes in direct measures of glycemia over the initial 2-wk period was significantly different from the corresponding correlations between direct measures of glycemia and fructosamine over this period (P less than .05-.01). Changes in GSA also correlated more closely than HbA1 or fructosamine did with direct measures of glycemia after 4 and 6 wk. The Spearman rank-correlation coefficient (rs) of absolute changes in GSA, fructosamine, and HbA1 after 2-6 wk ranged from 0.27 to 0.57, confirming that the three measures responded differently to changing glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of early diabetic nephropathy on very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) composition.

The procedure of discontinuous gradient ultracentrifugation (DGU) was used to characterize the influence of early diabetic nephropathy on the composition of very low density lipoprotein (VLDL, flotation density 60-400 Svedberg (Sf) units), low density lipoprotein (LDL, flotation density 0-12 Sf) and subfractions of intermediate density lipoprotein (IDL1 and IDL2, 20-60 and 12-20 Sf, respectively). Forty-six subjects with type 1 (insulin-dependent) diabetes and serum creatinine, less than 140 mumol/l were studied, of whom 23 consistently had normal rates of albumin excretion (AER less than 15 micrograms/min), and 23 had persistent albuminuria (AER 20.0-960.6 micrograms/min). The two groups were similar with respect to total serum lipids, glycaemic control, age and body mass. The composition (lipid, protein and phospholipid) and mass of VLDL, LDL and IDL2 was not appreciably altered by early nephropathy, but free and total cholesterol concentration in IDL1 (Sf 20-60) was increased (total cholesterol 0.68 (0.09) (mean (SE)) vs. 0.47 (0.07) mmol/l, and free cholesterol 0.27 (0.04) vs. 0.17 (0.03) mmol/l, both P less than 0.05). The explanation of these findings was probably an accumulation in the circulation of the remnants of chylomicron metabolism and/or intermediates in the conversion from VLDL to IDL1. In addition, there was a decrease in serum high density lipoprotein (HDL) cholesterol in early nephropathy (1.27 (0.06) vs. 1.38 (0.10) mmol/l, P less than 0.05), due to a decrease in the HDL2 cholesterol subfraction (P less than 0.05). These findings may in part explain the increased risk of premature atherosclerosis associated with the development of albuminuria.

Apolipoprotein E polymorphism and lipoproteins in insulin-treated diabetes mellitus.

Apolipoprotein E (apo E), a component of VLDL, HDL and chylomicron remnants, is inherited at a single genetic locus with 3 common alleles (epsilon 2, epsilon 3 and epsilon 4). epsilon 2 homozygosity is found in 0-2% of healthy populations, but in 75-100% of subjects with type III hyperlipoproteinaemia, in whom an increased prevalence of glucose intolerance has previously been reported. The lipoprotein abnormality associated with diabetes mellitus has features in common with type III hyperlipoproteinaemia and both conditions lead to accelerated atherogenesis with a similar anatomical distribution. We have therefore examined the frequency of apo E genotypes in 120 subjects with insulin-treated diabetes mellitus (ITDM) and 107 healthy controls, and examined the effect of apo E polymorphism on lipoproteins in the diabetic group. As in the general population, the apo E phenotype in ITDM was a significant determinant of the total serum and LDL cholesterol concentrations which were lowest in patients possessing the epsilon 2 allele, intermediate in those homozygous for epsilon 3 and highest in those with an epsilon 4 allele. The observed gene frequencies of epsilon 2 (0.091), epsilon 3 (0.780) and epsilon 4 (0.130) were similar to those of the healthy control group and those in the general population. However, there was an unexpected increase (P less than 0.0002) in epsilon 2 homozygosity of 6.7% compared to a prevalence of 0.8% predicted both from the Hardy-Weinberg equilibrium and the 0.9% prevalence observed in the healthy control group. This suggests either that epsilon 2 homozygosity increases susceptibility to the development of ITDM or that the two conditions are genetically linked.(ABSTRACT TRUNCATED AT 250 WORDS)

Microalbuminuria and associated cardiovascular risk factors in the community.

The prevalence of microalbuminuria and relationship to cardiovascular risk factors was examined in a cross-sectional community survey of cardiovascular risk factors. Microalbuminuria (when classified as albumin concentration greater than 20 micrograms/ml) was present in 6.3% of subjects but in conjunction with an albumin/creatinine ratio greater than 3.5 in only 2.2%. Diastolic blood pressure, prevalence of abnormal electrocardiographs, and to a lesser extent systolic blood pressure and fibrinogen concentration, were greater in those with albuminuria concentrations greater than 20 micrograms/ml. The strongest positive univariate correlates of albumin/creatinine ratios in those with detectable albuminuria were age, fibrinogen, blood pressure, total- and low density lipoprotein-(LDL) cholesterol, apo B and alcohol intake, whereas fasting insulin and insulin resistance were inversely correlated. Multiple regression analysis revealed that age, gender, systolic blood pressure and insulin resistance independently accounted for 37% of the variability in albumin/creatinine ratios. When those 10 subjects with microalbuminuria and albumin/creatinine ratios greater than 3.5 were matched with 20 with normoalbuminuria for age, gender and body mass index, the microalbuminuric subjects had significantly lower LDL cholesterol/apo B ratios and a tendency to lower high density lipoprotein (HDL) cholesterol and HDL cholesterol/apo A1 ratios. Microalbuminuria is uncommon in the general population, and is related to ageing, blood pressure and other vascular risk factors. It may reflect the presence of established cardiovascular disease.

Effects of treatment of hypertriglyceridaemia with gemfibrozil on serum lipoproteins and the transfer of cholesteryl ester from high density lipoproteins to low density lipoproteins.

Lipoprotein composition and cholesterol esterification, before and after treatment with gemfibrozil, have been examined in the fasting and postprandial state in nine patients with primary hypertriglyceridaemia who participated in a double-blind, placebo controlled study. After 8 weeks of treatment fasting serum triglycerides were reduced significantly from 6.05 mmol/l (range 2.48-10.99 mmol/l) to 1.76 mmol/l (range 1.16-11.90 mmol/l) (P less than 0.001). This was mainly due to a decrease in the triglyceride content of the Sf 12-20, 60-400 and Sf greater than 400 lipoprotein fractions (P less than 0.05). The Sf 0-12 fraction showed an increase in cholesteryl ester, free cholesterol, phospholipids and protein. Consistent with these findings there was a net increase in the mass concentration of the Sf 0-12 fraction (P less than 0.05) and a decrease in that of small very low density lipoproteins (Sf 20-60) (P less than 0.05). In the 8 patients in whom it was measured there was a 40% reduction in the rate at which cholesteryl esters derived from radiolabelled-free cholesterol appeared in very low density lipoprotein (VLDL) and low density lipoprotein (LDL) measured in an in vitro system (P less than 0.02), but serum lecithin:cholesterol acyl transferase (LCAT) activity was unchanged. At the end of each treatment phase (placebo or gemfibrozil) patients were given a mixed meal containing 100 g of fat. Treatment with gemfibrozil resulted in a reduction in serum triglyceride concentrations at all time points for at least 5 h after the meal (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus.

The activity of serum paraoxonase, an enzyme located on high-density lipoprotein, has been investigated in familial hypercholesterolaemia (FH) and insulin dependent diabetes mellitus (IDDM). Increases in total serum cholesterol and apolipoprotein B were present in both FH and IDDM compared to healthy controls and in the patients with IDDM, serum triglycerides were also raised. The serum HDL-cholesterol concentrations in controls and patients with FH and IDDM did not differ significantly. Serum paraoxonase activity was significantly lower in both the FH and IDDM populations than in controls (P less than 0.001 and P less than 0.01, respectively). 72% of the FH population and 67% of the IDDM population were in the lower half of the frequency distribution for serum paraoxonase (activity of less than 112 U/l). It is likely that the common factor related to low paraoxonase activity is hyperlipidaemia. It is possible that paraoxonase has a physiological role in lipid metabolism and that decreases in its activity may accelerate atherogenesis.

The effect of bezafibrate on very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) composition in type 1 diabetes associated with hypercholesterolaemia or combined hyperlipidaemia.

Lipoprotein composition was examined in type 1 diabetic subjects with hypercholesterolaemia +/- hypertriglyceridaemia during a 3-month double-blind placebo controlled assessment of bezafibrate therapy. The predominant effect was on lipoprotein lipid content. In those with hypercholesterolaemia alone, bezafibrate significantly reduced the cholesterol (particularly esterified cholesterol) and triglyceride content of large very low density lipoprotein (VLDL) (Svedberg flotation units (Sf) 60-400) in comparison to the placebo group (P less than 0.05), and a trend towards a reduction in free and esterified cholesterol within the intermediate density lipoprotein fraction (IDL) (Sf 12-20) was noted. Low density lipoprotein (LDL) composition was unaltered and in general phospholipid and protein concentrations and cholesteryl ester/protein ratios within the lipoprotein fractions were unaffected. Large VLDL cholesterol and triglyceride concentrations in those with combined hyperlipidaemia were significantly decreased following bezafibrate therapy, both in comparison to placebo-treated subjects and to baseline concentrations (P less than 0.05). An additional significant reduction in small VLDL (Sf 20-60) free cholesterol was recorded (P less than 0.05). Average reductions of large and small VLDL protein of 50-56% were not significant because of wide variation in responses. Bezafibrate had no effect on the abnormal composition of IDL and LDL, characteristic of Type 1 diabetes, regardless of whether or not hypertriglyceridaemia was associated with hypercholesterolaemia. Its major action was to lower VLDL lipid concentrations, but it may also reduce the lipid content of intermediate density lipoprotein in Type 1 diabetes.

A comparison of direct measures of glycaemia and glycated blood proteins in insulin-dependent diabetes mellitus.

We have studied associations between various direct measures of glycaemia and glycated blood proteins in 113 subjects with insulin-dependent diabetes mellitus (IDDM), and examined whether or not the 'fructosamine' assay results were affected by differing patient serum concentrations of lipids, albumin or C peptide. Serum fructosamine correlated less closely with HbA1 (r = 0.44) than did HbA1 with glycated serum albumin (GSA) (r = 0.68). Serum fructosamine and GSA also were poorly correlated (r = 0.48). Although fructosamine, HbA1 and GSA correlated to a similar degree with fasting blood glucose (r range 0.34 to 0.37), GSA was most closely related to mean blood glucose (r = 0.39 vs. 0.30-0.35) and the M value (a marker of diurnal glycaemic instability) (r = 0.42 vs. 0.33-0.35). The serum concentration of fructosamine was not significantly affected by a variation in serum cholesterol, but tended to be lower in subjects with moderate hypertriglyceridaemia (p = 0.05). The fructosamine assay may be altered by moderately lipaemic serum but is not affected by serum albumin concentration in normoalbuminaemic patients with IDDM. Our study indicates, however, that GSA is a more reliable marker of short-term glycaemic control in IDDM than fructosamine.

Validation of the Friedewald formula for the measurement of low density lipoprotein cholesterol in insulin-dependent diabetes mellitus.

The Friedewald formula has been widely used in the estimation of the serum LDL cholesterol concentration in diabetic patients. In patients with insulin-dependent diabetes we have compared the serum LDL cholesterol concentrations obtained when VLDL was isolated in the preparative ultracentrifuge and its cholesterol content directly determined with those when the 'Friedewald Formula' assumption that there is a fixed ratio between total serum triglycerides and VLDL cholesterol was used in the calculation of the LDL cholesterol value. Both methods gave similar results which were closely correlated (r = 0.98) with a slope of 0.98 on linear regression analysis for patients with serum triglycerides of less than 2.5 mmol/l. The inclusion of a small number of hypertriglyceridaemic patients (14%) had virtually no impact on these findings.

Precise measurement of glycated serum albumin by column affinity chromatography and immunoturbidimetry.

A precise and easy method for measuring glycated serum albumin using affinity chromatography and immunoturbidimetry on a centrifugal analyser, ensuring complete recovery of serum albumin is described.

Serum triglyceride and insulin levels are associated with erythrocyte sodium-lithium counter-transport activity in normoglycaemic individuals.

The relationship between erythrocyte sodium-lithium counter-transport activity, serum insulin, lipids and demographic factors was examined in 93 normoglycaemic predominantly normotensive individuals with mild fasting hypercholesterolaemia (greater than 5.2 mmol/l). The major significant univariate correlates of sodium-lithium counter-transport activity were fasting serum triglycerides, HDL cholesterol, the ratio of fasting glucose: insulin, apo A1, alcohol consumption and apo B. Stepwise multiple regression analysis revealed 24% of the variability in sodium-lithium counter-transport activity could be accounted for by independent contributions of fasting serum triglycerides, alcohol consumption, the fasting glucose/insulin ratio and apo A1 and ANOVA confirmed a significant relationship with fasting insulin measures that was independent of serum triglycerides (P less than 0.05). The relationship between erythrocyte sodium-lithium counter-transport activity and concentrations of serum triglycerides, HDL components, insulin and additionally alcohol consumption, could reflect the influence of those variables on erythrocyte structure and function.

Relationships between renin, aldosterone, blood pressure and renal function in hypertensive insulin-dependent diabetes mellitus.

A cross-sectional analysis of associations between total plasma renin (TPR) and aldosterone, blood pressure, renal haemodynamics, autonomic function and electrolyte balance was carried out in 35 hypertensive non-azotaemic insulin-dependent diabetics. Supine TPR was increased in 10 subjects and reduced in one, although erect TPR was increased in nine but reduced in 18 subjects. The supine to erect TPR gradient was greater than 40% in all cases. Supine and erect TPR correlated closely (r = 0.99, P less than 0.001). No correlation was found between TPR and age or blood pressure and multiple regression analysis failed to reveal independent predictors for TPR. Supine aldosterone was reduced in two subjects and increased in three, and erect aldosterone levels were reduced in three but increased in eight subjects. However, the postural aldosterone gradient was greater than 40% in only 20 cases. Supine and erect aldosterone correlated with each other (rs = 0.64, P = 0.001) but not with TPR. Aldosterone levels were most strongly related inversely to duration of diabetes, diabetic retinopathy, parasympathetic neuropathy and directly to diastolic blood pressure and glomerular filtration rate. Aldosterone levels correlated negatively with age. This was corrected for in multiple regression analysis which revealed an inverse relationship between supine aldosterone and serum potassium (P less than 0.05) and a direct one with renal plasma flow (P less than 0.007). Erect aldosterone was independently associated with duration of diabetes (P less than 0.005), systolic postural gradient (P less than 0.02), and the postural aldosterone gradient with the presence of parasympathetic neuropathy (P less than 0.004). The observation of elevated TPR in 10 subjects and the lack of relationship between TPR and other variables may reflect the overproduction of inactive relative to active renin in insulin-dependent hypertensive diabetics with autonomic dysfunction. The association between aldosterone and blood pressure, renal haemodynamics and electrolyte balance suggests that mineralocorticoids may be relevant to the natural history of hypertensive diabetic renal disease.

The relevance of persistent C-peptide secretion in type 1 (insulin-dependent) diabetes mellitus to glycaemic control and diabetic complications.

The effect of residual C-peptide secretion in longer standing IDDM on glycaemic control and the prevalence and evolution of complications over 2 years was evaluated. Thirty-one subjects with IDDM of 15.4 (1.5) years duration (mean SEM)) and residual C-peptide secretion, were matched for age, duration of diabetes and body mass index with 31 subjects without detectable C-peptide secretion. At trial entry and over 2 years, levels of HbA1, fructosamine and mean blood glucose were essentially similar in both groups. Levels of glycated albumin (GSA) were significantly higher in the C-peptide negative group after 3 and 9 months (P less than 0.05). An increased prevalence of proliferative retinopathy in the C-peptide negative group and of peripheral vascular disease in the C-peptide secretor group was apparent at entry to the study (both P less than 0.05), although no significant differences were observed after 1 or 2 years. There was no difference in the prevalence of peripheral or autonomic neuropathy, hypertension, nephropathy or ischaemic heart disease. Subjects with C-peptide concentrations greater than 0.100 pmol/ml at entry to this study had lower daily insulin requirements after 1 and 2 years, but behaved like the larger group with any detectable C-peptide secretion in all other respects. Residual C-peptide secretion was lost after 1 year in 7 patients, in whom glycaemic control during the year had been particularly poor. Insulin antibody titres were no different in the 2 groups at any time point. This study suggests that residual C-peptide secretion in longer standing IDDM confers the potential for limited improvements in glycaemic control. This effect appears to be insufficient to prevent the evolution of microvascular complications over a 2-year period. Residual C-peptide secretion and relative hyperinsulinaemia may be associated with an excess of peripheral vascular disease.

A cross-sectional evaluation of cardiovascular risk factors in coronary heart disease associated with type 1 (insulin-dependent) diabetes mellitus.

The contribution from lipoproteins, blood pressure, albuminuria and demographic variables to coronary heart disease in 90 adult subjects with and 172 without Type 1 diabetes mellitus was examined in order to investigate whether risk factors were of equivalent importance in diabetic and non-diabetic coronary heart disease. Coronary heart disease (CHD) was present in roughly 25% of subjects in each group. In Type 1 diabetes those with CHD had significantly higher levels of systolic blood pressure, albumin excretion, serum creatinine, triglycerides, VLDL cholesterol and C-peptide, and reductions in serum concentrations of HDL and HDL2 cholesterol, in comparison to those without. However, the prevalence of smokers, and concentrations of Lp(a), ApoB and fibrinogen were comparable. Blood pressure and HDL cholesterol were higher in the CHD group with Type 1 diabetes in comparison to the nondiabetic group with CHD, although LDL concentrations and the prevalence of Lp(a) concentrations > 200 mg/l were lower. Logistic regression analysis revealed the strongest independent predictors of CHD in Type 1 diabetes were serum triglycerides, systolic blood pressure, age, serum LDL cholesterol, and the daily insulin dosage, whereas in the non-diabetic control group HDL2 cholesterol, Lp(a), ApoA1 and ApoB, total serum cholesterol and body mass index were additional predictors. CHD in Type 1 diabetes appears to be most closely associated with increasing age and levels of blood pressure and total serum lipids. Apolipoproteins and albuminuria did not seem to be important independent predictors of CHD in Type 1 diabetes, whereas the former were more clearly associated with CHD in non-diabetic controls.

Simvastatin in non-insulin-dependent diabetes mellitus: effect on serum lipids, lipoproteins and haemostatic measures.

The clinical efficacy of the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase inhibitor simvastatin in the treatment of hypercholesterolaemia in non-insulin-dependent diabetes (NIDDM), was examined in a double-blind placebo-controlled study of 6 months in 70 patients with NIDDM (age 25-70 years), of whom 57 were randomised to placebo (29 patients) or simvastatin for 6 months, following a 3-month run-in on diet. Patients were hypercholesterolaemic (7.8 (7.6-8.0) (mean (95% confidence intervals)) mmol/l simvastatin vs. 8.0 (7.7-8.5) mmol/l placebo) and mildly hypertriglyceridaemic (2.6 (2.2-3.0) simvastatin vs. 2.9 (2.3-3.5) placebo). Other lipid measures and estimates of glycaemic control and haemostasis were similar in both groups. There were no significant changes in lipids, haemostatic factors, or measures of glycaemic control in the placebo treatment group. Conversely by the end of 24 weeks, simvastatin produced a 28% reduction in cholesterol (to 5.6 (5.0-6.2) mmol/l (P < 0.001)), a 38% reduction in LDL cholesterol (from 5.5 (5.4-5.6) mmol/l to 3.4 (2.8-4.0) mmol/l, P < 0.001), a 15% reduction in triglyceride (to 2.2 (1.8-2.6) mmol/l, P < 0.05, and a 9% rise in HDL (from 1.16 (1.07-1.25) to 1.23 (1.14-1.32) mmol/l, P < 0.05). Improvements in apolipoprotein B (apo B) (-28%, P < 0.001), the LDL cholesterol to apo B ratio (-20%, P < 0.001), and apo A1 (+15%, P < 0.001) were recorded. There were no effects upon fibrinogen, factor VII activity, factor VIII activity, or measures of glycaemic control (fasting glucose, insulin, C-peptide, or HbA1).(ABSTRACT TRUNCATED AT 250 WORDS)

Does the measurement of serum fructosamine accurately reflect levels of glycated albumin in insulin-dependent diabetes?

We have measured serum glycated albumin (GSA) by affinity chromatography and immunoturbidimetry, and serum fructosamine using a Cobas FARA analyser in blood samples from 37 type I diabetics and 21 healthy controls. Random blood glucose and glycated haemoglobin levels were also measured. Glycated haemoglobin (HbA1) correlated with glycated albumin and fructosamine in the diabetic group. A less clear relationship was found between glycated albumin and fructosamine. HbA1, GSA and fructosamine correlated poorly with random blood glucose levels. These data indicate that serum fructosamine levels do not accurately reflect those of glycated albumin, as has recently been suggested, in type I insulin-dependent diabetics where glycaemic control fluctuates more than in type II diabetics. It is postulated that the two methods reflect varying glycaemic levels to a different degree, thereby accounting for the disparity.

Platelet and plasma vasoactive amines in type 1 (insulin-dependent) diabetes mellitus with and without vascular disease.

Platelet and plasma vasoactive amine concentrations were measured in healthy controls and in type 1 (insulin-dependent) diabetic patients with or without vascular disease. Platelet concentrations of serotonin and noradrenaline were similar in all groups and were unrelated to age or gender, or to duration of diabetes, blood pressure, glycaemia or renal function in the diabetic subjects. Plasma concentrations of serotonin in the diabetic groups were comparable (118 +/- 16 (mean +/- SEM) and 127 +/- 21 pmol/mL), and were significantly higher in comparison to the healthy controls (66 +/- 12 pmol/mL, P = 0.002).