Factors Related to the Electric Taste Threshold in Type 1 Diabetic Patients

To specify the factors related to taste function in Type 1 diabetes mellitus, 50 diabetic out-patients and 50 control subjects paired for age and sex were screened for taste disorders. None of them consumed significant amounts of alcohol, smoked, or had disease or took drugs capable of altering taste. Taste was studied with electrogustometry, retinopathy was detected by fluorescein angiography, nephropathy by measurement of albuminuria and microalbuminuria, peripheral neuropathy by electroneurography and electromyography, and autonomic neuropathy by cardiovascular function tests. The electrogustometric threshold was, on average, significantly higher in the diabetic group (133 ± 30 μA) than in the control group (29 ± 9 μA; p < 0.001). Electric hypogeusia (electrogustometric threshold > 100 μA) was found among 54% of the diabetic patients vs 2% of the control subjects (p < 0.001). In the diabetic group, the electrogustometric threshold was associated with complications of diabetes, especially with peripheral neuropathy (210 ± 24 vs 90 ± 22 μA; p < 0.001) and microalbuminuria (185 ± 25 vs 86 ± 21 μA; p < 0.01). It was correlated with age (r = 0.37; p < 0.01) and duration of diabetes (r = 0.52; p < 0.001) but not with HbA_1c (r = ?0.04). Using multivariate analysis, duration of diabetes and peripheral neuropathy had the strongest association with taste impairment. These results support previous findings, suggesting that taste impairment is a degenerative complication of diabetes mellitus.     

Risk factors for mortality in Type II (non-insulin-dependent) diabetes: evidence of a role for neuropathy and a protective effect of HLA-DR4

Summary To test the hypothesis that interaction between genetic, immunological, clinical and metabolic risk factors influences the outcome of Type II (non-insulin-dependent) diabetes mellitus, we examined which of the above factors present at baseline were associated with mortality in 134 Type II diabetic patients followed for 9 years. Thirty-eight patients (29 %) died during the follow-up period; the majority of whom (68 %) died from cardiovascular disease. At baseline, the deceased patients had higher HbA_{1 c} values (p = 0.002), higher LDL-triglycerides (p = 0.007), lower HDL-cholesterol (p = 0.007), higher non-esterified fatty acid (NEFA) concentrations (p = 0.014), and higher albumin excretion rate (p < 0.0001) than the patients who survived. In addition, the frequency of HLA-DR4 (21 vs 39 %, p = 0.048) and of parietal cell antibodies (5 vs 14 %, p = 0.016) were decreased in the deceased as compared to the living patients. Patients who died during follow-up also had more retinopathy (42 vs 16 %, p = 0.002), neuropathy (57 vs 23 %, p < 0.001), microalbuminuria (45 vs 6 %, p < 0.0001), coronary heart disease (50 vs 13 %, p < 0.0001), and peripheral vascular disease (27 vs 9 %, p = 0.005) at baseline than patients who survived. In a multiple logistic regression analysis macroangiopathy (p = 0.004), neuropathy (p = 0.007), HbA_{1 c} (p = 0.018) and albumin excretion rate (p = 0.016) were independent risk factors for death. In patients free of cardiovascular disease at baseline, conventional risk factors such as LDL-cholesterol (p = 0.005) and age (p = 0.003) were associated with subsequent development of cardiovascular disease. In conclusion, in addition to coexisting macroangiopathy, increased albumin excretion rate, poor glycaemic control and neuropathy are risk factors for cardiovascular mortality in patients with Type II diabetes. The presence of HLA-DR4 and signs of autoimmunity may be associated with decreased risk of cardiovascular disease. [Diabetologia (1998) 41: 1253–1262] Received: 29 December 1997 and in revised form: 27 April 1998     

Immunogenetic heterogeneity in Type 1 (insulin-dependent) diabetes among Japanese — HLA antigens and organ-specific autoantibodies

Summary HLA phenotypes and haplotypes in relation to organ-specific autoantibody responses were studied in 82 Japanese patients with Type 1 (insulin-dependent) diabetes. HLA-DRw9 antigen and HLA phenotype of DRw9/X (X: not DR4) were increased in patients with organ-specific autoantibodies other than islet cell antibody (CP<0.02, RR=4.02 and p<0.05, RR=2.30, respectively); whereas HLA-DR4 antigen and HLA phenotype of DR4/X (X: not DRw9) were increased in those without the autoantibodies (CP<0.001, RR=3.95 and p<0.01, RR=2.46, respectively). HLA haplotype of Bw61-DRw9 was increased in patients with the autoantibodies (p<0.005, RR=4.94), and HLA haplotype of Bw54-DR4 was increased in those without the autoantibodies (p<0.001, RR=5.52). The relative risk of HLA-DR4/DRw9 was the highest among all HLA-DR phenotypes or genotypes in patients either with or without the autoantibodies. No association was, however, found between the incidence of islet cell antibody and HLA-DR phenotypes. These findings suggest that Type 1 diabetes among Japanese is immunogenetically heterogeneous as is Type 1 diabetes among Caucasians; and the differences in HLA-association of Type 1 diabetes among ethnic groups might give a clue to understanding of a role of HLA-antigens in the development of Type 1 diabetes.     

Factors associated with progression to macroalbuminuria in microalbuminuric Type 1 diabetic patients: the EURODIAB Prospective Complications Study

Aims/hypothesis Type 1 diabetic patients who develop microalbuminuria are clearly disadvantaged in terms of their risk of morbidity and mortality from renal and cardiovascular diseases. It is therefore important to identify potential factors that can predict progression to macroalbuminuria.Methods This is a 7-year follow-up study of 352 microalbuminuric Type 1 diabetic patients from 31 European centres. Risk factors at baseline were compared in patients who progressed to macroalbuminuria and in patients who remained microalbuminuric or reverted to normoalbuminuria. Risk factors and albumin excretion rate (AER) were measured centrally.Results Over 7.3 years, 13.9% of the microalbuminuric patients progressed to macroalbuminuria, 35.5% remained microalbuminuric and 50.6% reverted to normoalbuminuria. Independent baseline risk factors for progression to macroalbuminuria were HbA₁c (7.9% vs 6.8%, p=0.004), AER (64.4 vs 44.9 µg/min, p=0.0001) and—after adjusting for diabetes duration, HbA₁c and AER—body weight (72 vs 67 kg, p=0.05). Independent factors associated with regression to normoalbuminuria were diabetes duration (15 vs 18 years, p=0.004), AER (37.2 vs 44.9 µg/min, p=0.0001) and—after adjusting for diabetes duration, HbA₁c and AER—waist-to-hip ratio (0.83 vs 0.86, p=0.05) and incidence of peripheral neuropathy at baseline (24% vs 38%, p=0.001). Blood pressure and smoking did not emerge as risk factors at baseline for the outcome of microalbuminuria.Conclusions/interpretation A significant fraction of microalbuminuric Type 1 diabetic patients will progress to overt proteinuria. Patients with higher AER values, sub-optimal metabolic control, excess body fat and peripheral neuropathy may carry a particularly high risk of clinical nephropathy requiring aggressive therapeutic intervention.Abbreviations AER albumin excretion rate - CVD cardiovascular disease - Gamma GT gamma-glutamyltransferase - OR odds ratio - PCS Prospective Complications Study - RR relative risk - SERR standardised estimates of relative risk - SREs standardised regression effects - vWF von Willebrand Factor     

Prothrombotic and Antithrombotic Factors are Elevated in Patients with Type 1 Diabetes Complicated by Microalbuminuria

Increased urinary albumin loss in patients with Type 1 diabetes is associated with accelerated atherosclerosis. Prothrombotic factors known to be associated with cerebrovascular and coronary artery disease in the general population, and antithrombotic factors, were studied in 52 patients with Type 1 diabetes and varying urinary albumin loss and 24 non-diabetic control subjects. Fibrinogen increased from 2.5 g I_-1 (95 % confidence interval 2.3–2.8) in control subjects and 2.8 g I_-1 (2.6–3.0) in diabetic patients without microalbuminuria to 3.1 g I_-1 (2.7–3.5) with microalbuminuria (p < 0.005 vs control; p < 0.001 vs without microalbuminuria). Factor VIIc increased from 81 % (75–86 % in non-diabetic control subjects and 84 % (78–90 %) in diabetic patients without microalbuminuria to 103 % (89–117 %) with microalbuminuria (p < 0.005 vs control; p < 0.05 vs without microalbuminuria) and 118% (86–150%) with albuminuria (p < 0.005 vs control and p < 0.001 vs without microalbuminuria). Levels of the antithrombotic factors protein C, protein S, and antithrombin III also rose in the diabetic patients with evidence of renal damage. Elevation of prothrombotic factors has been associated with increased risk of microvascular disease, whereas elevation of antithrombotic factors has no known protective effect. Therefore, this pattern of alteration of haemostatic factors in diabetic renal disease may contribute to the increased risk of vascular disease associated with both microalbuminuria and albuminuria.     

Endothelium-dependent and independent vasodilation studied at normoglycaemia in Type I diabetes mellitus with and without microalbuminuria

Aims/hypothesis. We examined whether endothelial function is impaired in patients with Type I (insulin-dependent) diabetes mellitus under conditions of near-normoglycaemia compared with age-matched healthy control subjects. Our aim was to determine whether microalbuminuria is associated with endothelial dysfunction in Type I diabetes. Methods. Endothelial function, measured as post-ischaemic flow-mediated dilatation of the brachial artery using ultrasound, was compared among 17 microalbuminuric and 17 normoalbuminuric diabetic patients, and 17 control subjects. Glyceryl trinitrate-mediated dilatation of the brachial artery was used to measure endothelium-independent function. All diabetic patients were studied at near-normoglycaemia, using insulin and 5 % dextrose infusions to maintain blood glucose between 3.5 and 8.0 mmol/l. Results. Flow-mediated dilatation was significantly lower in microalbuminuric diabetic patients (3.2 ± 0.3 %) compared with normoalbuminuric diabetic patients (5.4 ± 0.6 %) and control subjects (7.9 ± 0.6 %, p < 0.001). Normoalbuminuric diabetic patients also had significantly lower flow-mediated dilatation than control subjects (p = 0.01). Glyceryl trinitrate mediated dilatation was significantly lower in the microalbuminuric patients compared with the control subjects (11.9 ± 1.1 % vs 20.0 ± 1.2 %, p = 0.001). Albumin excretion rate and glycated haemoglobin showed a significant negative independent correlation with flow-mediated dilatation (both p < 0.05). Conclusion/interpretation. Type I diabetic patients show endothelial dysfunction at near-normoglycaemia compared with the control subjects, and this abnormality is more marked in diabetic patients with microalbuminuria. Endothelial dysfunction in Type I diabetes is related to the albumin excretion rate and glycaemic control. The presence of endothelial dysfunction in normoalbuminuric diabetic patients suggests it could precede microalbuminuria as an early risk marker for cardiovascular disease. [Diabetologia (2001) 44: 593–601] Received: 6 November 2000 and in revised form: 11 January 2001     

Current status of Type 2 (non-insulin-dependent) diabetic subjects on dialysis therapy in Japan

Summary According to a national survey of dialysis patients in Japan conducted by the Japanese Society for Dialysis Therapy, there were 1,033 patients on dialysis in the Shiga area which has a population of about 1.2 million. Of these 1,033 dialysis patients 140 were the result of diabetic nephropathy. From four hospitals affiliated to Shiga University of Medical Science the medical records of 90 diabetic subjects on dialysis therapy were reviewed and various clinical parameters were analysed and compared with those of patients with chronic glomerulonephritis. Since only one patient had Type 1 (insulin-dependent) diabetes, the remaining 89 with Type 2 (non-insulin-dependent) diabetes were used for this study. The significantly different variables between patients with Type 2 diabetes and chronic glomerulonephritis were age (60.4 vs 54.6 years,p<0.05), BMI (22.4 vs 20.6 kg/m²,p<0.001), cardiothoracic ratio (56.4 vs 53.3%,p<0.001), mean blood pressure (110 vs 117 mm Hg,p<0.05), serum creatinine (9.0 vs 11.5 mg/dl,p<0.001), serum urea-N (98.2 vs 115.5 mg/dl,p<0.001), serum total protein (6.0 vs 6.5 g/dl,p<0.001) and serum albumin (3.5 vs. 3.9 g/dl,p<0.001). Serum levels of cholesterol and triglyceride were not significantly different between two groups, though the prevalence of electrocardiogram abnormalities, oedema, neuropathy, myocardial infarction and cerebrovascular diseases was significantly higher in the Type 2 diabetic group. These results suggested that Type 2 diabetic patients with end-stage renal disease were older, more malnurished, fluid overloaded and multi-morbid as a result of vasculopathy and neuropathy. However, the analysis of causes of death in Type 2 diabetic patients (n=24) and patients with chronic glomerulonephritis (n=26) failed to provide evidence of higher risk of cardiac death in the Type 2 diabetic group compared to the group with chronic glomerulonephritis (37.5 vs 34.6%, NS). In the Type 2 diabetic patients on dialysis therapy, malnutrition, fluid overload and neuropathy appeared to be significant factors influencing the outcome of the therapy, while in patients with chronic glomerulonephritis, age and vascular morbidities were considered to be major risk factors for the prognosis.     

Diurnal Variation in Blood Pressure in Insulin-dependent Diabetic Smokers and Non-smokers with and without Microalbuminuria

In subjects with essential hypertension, loss of the normal nocturnal dip in blood pressure is associated with a greater risk of developing end-organ complications. In subjects with diabetes, smoking carries a similar association. To assess whether these factors may have an aetiological and synergistic role in the vascular complications of diabetes, 24-hour blood pressure monitoring was performed in insulin-dependent diabetic (IDDM) patients with normal albumin excretion (n = 19) and microalbuminuria (n = 21) of comparable age and duration of diabetes, and with no evidence of autonomic neuropathy or hypertension. The potential influence of smoking was examined by subdividing the groups, depending on smoking status. Ten of the microalbuminuric group and 9 of the normoalbuminuric group were current smokers, the remaining patients never having smoked. There was a significant difference between mean (±SD) daytime vs nocturnal blood pressure in patients with normal albumin excretion (114 ± 3/70 ± 4 vs 102 ± 3/62 ± 3 mmHg; p < 0.001) and microalbuminuria (109 ± 5/75 ± 5 vs 101 ± 3/65 ± 4 mmHg; p < 0.001) but mean blood pressure values did not differ significantly between the groups. A similar fall in nocturnal blood pressure was found in smokers and non-smokers with and without microalbuminuria (p < 0.001), but there was no difference between the mean blood pressure values in the different subgroups. In conclusion, normotensive IDDM patients, who do not have autonomic neuropathy, retain a significant diurnal variation in blood pressure, irrespective of smoking habit or presence of microalbuminuria. © 1997 by John Wiley & Sons, Ltd.     

Impact of non‐alcoholic fatty liver disease on microalbuminuria in patients with prediabetes and diabetes

Background: It is unknown whether microalbuminuria is associated with non‐alcoholic fatty liver disease (NAFLD) among patients with prediabetes and type 2 diabetes mellitus (DM). This study investigated the association of NAFLD with microalbuminuria among patients with prediabetes and diabetes. Methods: We evaluated 1361 subjects who had an abnormal oral glucose tolerance test (OGTT) on routine screening. All participants were divided into two groups, prediabetes and newly diagnosed type 2 DM, and the association of NAFLD with metabolic parameters on microalbuminuria was analysed. Results: The patients with NAFLD had higher prevalence rates of microalbuminuria (6.3% vs 19%; P= 0.001 in prediabetes, 4.5% vs 32.6%; P < 0.001 in diabetes) and also had a greater albumin‐to‐creatinine ratio (14.6 ± 52.0 µg/mg Cr vs 27.7 ± 63.9 µg/mg Cr; P= 0.051 in prediabetes, 11.4 ± 21.4 µg/mg Cr vs 44.7 ± 76.4 µg/mg Cr; P < 0.001 in diabetes) than those without NAFLD. The logistic regression analysis showed that NAFLD was associated with increased rates of microalbuminuria (odds ratio 3.66; 95% confidence interval (CI) 1.31–10.20, P= 0.013 in prediabetes, odds ratio 5.47; 95% CI 1.01–29.61, P= 0.048 in diabetes), independently of age, sex, body mass index, waist circumference, liver enzymes, lipid profiles, HbA1c, insulin resistance as estimated by homeostasis model assessment, hypertension, smoking status and the metabolic syndrome. Conclusions: The results of our study revealed a strong relationship between microalbuminuria and NAFLD in the patients with prediabetes and newly diagnosed diabetes. Further studies are required to confirm whether NAFLD is a predictor of the development of microalbuminuria in patients with prediabetes and diabetes.     

Hydroxyproline Excretion is Increased in Diabetes Mellitus and Related to the Presence of Microalbuminuria

Increased fracture frequency and low bone mass have each been reported in patients with diabetes. To see if these were related to increased bone resorption we have measured the urinary excretion of hydroxyproline in 73 patients with Type 1 (insulin-dependent) diabetes, 67 patients with Type 2 (non-insulin-dependent) diabetes, and 75 control subjects. Hydroxyproline excretion was increased in both types of diabetes: Type 1: 21 (10–36) (median (IQR) μmol mmol creatinine^?1; Type 2: 25 (13–43) μmol mmol creatinine^?1; control: 10 (6–22) μmol mmol creatinine^?1 (p < 0.0001 and < 0.0002, respectively). Hydroxyproline excretion was not related to age, duration of diabetes or blood glucose control. Neither was it different in patients with or without retinopathy, neuropathy and macrovascular disease. However it was higher in patients with microalbuminuria at 35 (20–53) μmol mmol creatinine^?1 than in those with normal protein excretion (25(13–37) μmol mmol creatinine^?1 p = 0.03) or those with established proteinuria (18(8–26) μmol mmol creatinine^?1 p = 0.001). We conclude that there is evidence of increased bone resorption in diabetes and that this is related to alterations in renal function.     

Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus

Aims/hypothesis. To determine causes of weight gain during insulin therapy with and without metformin in Type II (non-insulin-dependent) diabetes mellitus. Methods. Twenty-six patients with Type II diabetes (body mass index 28 ± 1 kg/m²) were treated with insulin alone (n = 13) or insulin and with metformin (n = 13). Components of energy balance (basal metabolic rate, energy intake, glucosuria) were measured at 0 and 12 months. Results. Glycaemic control improved similarly in patients using (HbA_{1 c} 10.5 ± 0.3 vs 7.6 ± 0.2 %, p < 0.001) and not using (10.2 ± 0.3 vs 7.8 ± 0.3 %, p < 0.001) metformin. The metformin group required 47 % less insulin than the group not using metformin (p < 0.001). Body weight increased by 3.8 ± 0.8 and 7.5 ± 1.6 kg (p < 0.05), respectively. Basal metabolic rate and glucosuria were similar at 0 and 12 months in both groups but the metformin group decreased energy intake by 1.12 ± 0.46 MJ/day, whereas it remained unchanged in the other group (0.15 ± 0.42 MJ/day). Changes in body weight and glycaemia were statistically significant independent determinants of basal metabolic rate. Their change in opposite directions explained why basal metabolic rate remained unchanged. Conclusion/interpretation. Improved glycaemia promotes weight gain by decreasing both basal metabolic rate and glucosuria. Use of metformin decreases weight gain by reducing energy intake and is therefore a useful adjunct to insulin therapy in patients with Type II diabetes. [Diabetologia (1999) 42: 406–412] Received: 3 September 1998 and in final revised form: 4 December 1998     

Cerebral Glucose Metabolism in Type 1 Diabetic Patients

To evaluate whether cerebral glucose metabolism is impaired in diabetes the [¹⁸F]–2–deoxy–2–fluoro-d-glucose method and positron emission tomography were used to determine the regional cerebral metabolic rate of glucose in 12 healthy subjects, 8 newly diagnosed Type 1 diabetic patients, 6 Type 1 diabetic subjects without peripheral neuropathy, and 7 Type 1 diabetic patients with symptomatic peripheral neuropathy, all of whom were men. In addition, multimodal evoked potentials were assessed. Cerebral glucose consumption was significantly reduced in the group with neuropathy as compared with the newly diagnosed diabetic patients and the healthy subjects (26.9 ± 1.0 vs 33.9 ± 1.9 and 32.5 ± 1.1 ±mol 100 g^-1 min^-1; p<0.05), while in the patients without neuropathy it was 30.2 ± 2.5 ±mol 100 g^-1 min^-1 (NS vs the remaining groups). There were no significant differences between the groups regarding brainstem auditory and visual evoked potentials. No relationship was noted between cerebral glucose metabolism and P300 latency of event-related potentials as an index of cognitive function, but there was an inverse correlation with age (r = -0.42; p < 0.05) and duration of diabetes (r = -0.67; p < 0.05). These results suggest that cerebral glucose metabolism is normal at the time of diagnosis of Type 1 diabetes, but may become altered with both increasing duration of diabetes and age in the absence of central conduction deficits or cognitive dysfunction. Diabetic neuropathy may constitute a possible additional correlate of reduced cerebral glucose consumption.     

Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study

Summary The EURODIAB IDDM Complications Study involved the examination of 3250 randomly selected insulin-dependent diabetic patients, from 31 centres in 16 European countries. Part of the examination included an assessment of neurological function including neuropathic symptoms and physical signs, vibration perception threshold, tests of autonomic function and the prevalence of impotence. The prevalence of diabetic neuropathy across Europe was 28 % with no significant geographical differences. Significant correlations were observed between the presence of diabetic peripheral neuropathy with age (p < 0.05), duration of diabetes (p < 0.001), quality of metabolic control (p < 0.001), height (p < 0.01), the presence of background or proliferative diabetic retinopathy (p < 0.01), cigarette smoking (p < 0.001), high-density lipoprotein cholesterol (p < 0.001) and the presence of cardiovascular disease (p < 0.05), thus confirming previous associations. New associations have been identified from this study – namely with elevated diastolic blood pressure (p < 0.05), the presence of severe ketoacidosis (p < 0.001), an increase in the levels of fasting triglyceride (p < 0.001), and the presence of microalbuminuria (p < 0.01). All the data were adjusted for age, duration of diabetes and HbA_1c. Although alcohol intake correlated with absence of leg reflexes and autonomic dysfunction, there was no overall association of alcohol consumption and neuropathy. The reported problems of impotence were extremely variable between centres, suggesting many cultural and attitudinal differences in the collection of such information in different European countries. In conclusion, this study has identified previously known and new potential risk factors for the development of diabetic peripheral neuropathy. [Diabetologia (1996) 39: 1377–1384] Received: 14 December 1995 and in revised form: 27 June 1996     

Growth Hormone Levels in Patients with Type 1 Diabetes are Age Related

Possible effects of age on the growth hormone (GH) levels in Type 1 diabetes were examined. The study was performed in 71 patients with Type 1 diabetes (40 C-peptide negative (CpN), without residual beta cell activity; 31 C-peptide positive (CpP), with preserved beta cell activity) and 11 healthy subjects. The patients and controls were divided into three age groups (A = 21–30; B = 31–40; C = 41–50 years). Blood glucose and growth hormone (GH) were measured at hourly intervals during 24 h in all subjects in hospital conditions. GH levels decreased significantly with age in patients with Type 1 diabetes (mean 24-h GH group A: 7.3 ± 1.0, group B:5.3 ± 0.6, group C:3.7 ± 0.4 mU 1^?1; A vs C: p = 0.0007; B vs C: p = 0.03). In all age groups GH levels were significantly higher in CpN than either in CpP diabetic patients or controls (group A CpN: 8.3 ± 1.2, CpP: 4.7 ± 1.0, controls: 2.2 ± 0.3 mU 1^?1; p < 0.001; group B CpN: 7.3 ± 0.8, CpP: 3.2 ± 0.5, controls: 1.6 ± 1.0 mU 1^?1; p < 0.0002; group C CpN: 5.2 ± 0.5, CpP: 2.5 ± 0.4, controls: 1.4 ± 0.4 mU 1^?1; p < 0.001). Mean GH levels were significantly higher in C-peptide positive patients than in controls in all age groups (p < 0.001). GH levels decreased with age in patients with diabetes and controls, but the decrease was significant only in patients with diabetes (A vs C CpN: p = 0.018, CpP: p = 0.026). We conclude that age is a factor in addition to residual beta cell activity, which influences the magnitude of GH hypersecretion in Type 1 diabetes.     

Frequency and Symptoms of Hypoglycaemia Experienced by Patients with Type 2 Diabetes Treated with Insulin

This study ascertained the prevalence of severe hypoglycaemia and loss of awareness of hypoglycaemia in patients with Type 2 diabetes treated with insulin. One hundred and four sequentially selected Type 2 diabetic patients were compared with 104 patients with Type 1 diabetes who were matched for duration of insulin therapy. The patients were interviewed using a standardized questionnaire. During treatment with insulin, 18 Type 2 patients had experienced fewer than two episodes of hypoglycaemia, while 86 had experienced two or more episodes; 80 (93%) reported normal awareness, six (7%) reported partial awareness, and none had absent awareness of hypoglycaemia. All 86 Type 1 diabetic patients matched to the 86 Type 2 patients had experienced multiple episodes of hypoglycaemia; 71 (83%) had normal awareness, 14 (16%) had partial awareness and one patient (1%) reported absent awareness of hypoglycaemia. The Type 1 patients who had altered awareness of hypoglycaemia had longer duration of diabetes and insulin therapy (normal awareness: 5 (1–17) years (median (range)) vs partial awareness: 9 (3–18) years, p < 0.01). Similarly, Type 2 patients with altered awareness had longer duration of diabetes (normal awareness: 11 (2–25) years vs partial awareness: 19 (8–24) years, p < 0.02) and had received insulin for longer (normal awareness: 3 (1–18) years vs partial awareness: 12 (6–17) years, p < 0.001). Severe hypoglycaemia in the preceding year had occurred with a similar prevalence in the Type 2 patients (9 (10%)) and Type 1 patients (14 (16%)), but was more frequent in those patients with partial awareness both in Type 1 patients (normal awareness: 3 (4%) vs partial awareness: 11 (73%), p < 0.001) and in Type 2 patients (normal awareness: 3 (4%) vs partial awareness: 6 (100%), p < 0.001). Although the symptoms of hypoglycaemia were idiosyncratic in individual Type 2 patients, the range and prevalence of specific symptoms were similar to those described by the patients with Type 1 diabetes.     

Oxidative stress could precede endothelial dysfunction and insulin resistance in Indian Mauritians with impaired glucose metabolism

Aims/hypothesis. To measure oxidative stress, endothelial dysfunction and insulin resistance in Indian Mauritians at different stages of development of Type II (non-insulin-dependent) diabetes mellitus. Methods. Plasma total 8-epi-PGF₂α, an indicator of oxidative stress, was determined in age-matched subjects with normal glucose metabolism (n = 39), impaired glucose tolerance (n = 14), newly diagnosed diabetes (n = 8) and established diabetes (n = 14). Plasma glucose and insulin were measured at baseline and 2 h following an oral glucose tolerance test. Endothelial function was assessed by non-invasive digital pulse wave photoplethysmography. Results. Plasma 8-epi-PGF₂α increased in subjects with impaired glucose tolerance (p < 0.05) compared with control subjects, and was even higher in newly diagnosed diabetic patients (p < 0.01) and established (p < 0.01) diabetic patients. A tendency towards reduced endothelial function in subjects with impaired glucose tolerance became significant in patients with newly diagnosed and established diabetes (p < 0.01), and was correlated with 8-epi-PGF₂α (r = 0.36, p < 0.01). Insulin resistance (homeostasis model assessment) did not change in subjects with impaired glucose tolerance compared with control subjects, but increased in newly diagnosed (p < 0.01) and established (p < 0.001) diabetic subjects. The 8-epi-PGF₂α was correlated with fasting glucose (r = 0.50, p < 0.001), triglycerides (r = 0.40, p < 0.001) and insulin resistance (r = 0.35, p < 0.001). Conclusion/interpretation. Oxidant stress is an early event in the evolution of Type II diabetes and could precede the development of endothelial dysfunction and insulin resistance. [Diabetologia (2001) 44: 706–712 Received: 1 November 2001 and in revised form: 14 February 2001     

Higher Levels of Microproteinuria in Asian Compared with European Patients with Diabetes Mellitus and Their Relationship to Dietary Protein Intake and Diabetic Complications

Asian patients with diabetes have a higher prevalence of renal disease than their European counterparts. The aim of the study was to investigate the pattern of the renal excretion of proteins in 70 Asian and 70 European patients with diabetes and to relate it to dietary intake of protein and prevalence of diabetic complications. Compared with matched Europeans, Asian patients had an increased urinary excretion of albumin and transferrin (p < 0.02) with 14 Asians and 6 Europeans having significant microalbuminuria (> 30 μg min^?1). In 12 Asians and all 6 Europeans this was associated with complications from diabetes, particularly vascular. Asian patients had significantly more ischaemic heart disease (p < 0.001) but less neuropathy (p < 0.001) and retinopathy (p < 0.05) than their matched European counterparts. Asian diets were lower in protein (median (range) Asian vs European: 12.5% (6–29%) vs 19% (11–27%); p <0.01) and carbohydrate but higher in fat than European diets. There was no correlation between dietary protein intake and excretion of any of the urinary proteins measured. However, a significant correlation was found in Asians between protein intake and length of residence in the UK (p < 0.005). Unless ways to reduce complications can be found then future allocation of resources will need to take this into consideration in areas with large Asian communities.     

Detection of monocyte-derived microparticles in patients with Type II diabetes mellitus

Aims/hypothesis. The role of plasma monocyte-derived microparticles (MDMPs) and platelet-activation markers (platelet-derived microparticle [PDMP], platelet-bound CD62P [plt-CD62P], and platelet-bound CD63 [plt-CD63]) in diabetic vascular complications is not clear. We measured and compared plasma concentrations of MDMPs and the platelet-activation markers to investigate their possible contribution to diabetic vascular complications. Methods. Activated platelets and microparticles (PDMP and MDMP) were analysed by flow cytometry. Concentrations of serum sE-selectin were measured with enzyme-linked immunosorbent assay. Results. The concentration of MDMPs in diabetic patients was higher than in normal subjects. We found no differences in the binding of anti-GPIIb/IIIa and anti-GPIb monoclonal antibodies between groups. There were differences, however, in the concentrations of PDMPs, plt-CD62P, and plt-CD63 between Type II (non-insulin-dependent) diabetes mellitus patients and control subjects (PDMPs: 585 ± 25 vs 263 ± 9, p < 0.01; plt-CD62P: 28.1 % ± 1.4 % vs 9.4 % ± 0.6 %, p < 0.001; plt-CD63: 28.1 % ± 1.4 % vs 8.6 % ± 0.5 %, p < 0.001). Amounts of MDMPs correlated positively with these platelet activation markers, and the relation between PDMP and MDMP was the most significant. The concentration of MDMP in patients who had diabetes complicated with nephropathy, retinopathy, or neuropathy was higher than in those without diabetes-related complications. The increase in MDMP was particularly significant in patients with nephropathy. Concentrations of sE-selectin were higher in Type II diabetes patients than in control subjects, and correlated with MDMP, PDMP, plt-CD62P, and plt-CD63 levels in nephropathy patients. Conclusion/interpretation. In Type II diabetes patients, we detected increased activation of monocytes, which could have been stimulated by activated platelets and PDMPs. Because the activation of monocytes is associated with vascular endothelial damage, high concentrations of MDMPs could indicate vascular complications in diabetes patients, especially those who have diabetes-related nephropathy. [Diabetologia (2002) 45: ▪–▪] Received: 21 May 2001 and in revised form: 13 November 2001     

Post-exercise Albuminuria Does Not Predict Microalbuminuria in Type 1 Diabetic Pantients

To investigate whether post-exercise urinary albumin excretion in Type 1 diabetic children and adolescents may prospectively predict the development of microalbuminuria, we have assessed post-exercise urinary albumin excretion before and after 6.2 ± 1.7 years of follow-up in 66 diabetic children and adolescents. Post-exercise urinary albumin excretion rose significantly above the pre-exercise values in diabetic patients by 2.7 (-3.8 to 84.2) μ min^?1 (p < 0.001) and in a group of 9 healthy individuals by 3.9 (-0.7 to 13.7) μg min^?1 (p < 0.02) without significant differences betbeen groups. Post-exercise albuminuria was greater in postpubertal than prepubertal 9.8 vs 4.3 μg min^?1 (p < 0.03) and pubertal 9.8 vs 6.0 μg min^?1 (p < 0.02) patients; post-exercise changes in urinary albumin excretion were also positively related to glycated haemoglobin (r = 0.293; p < 0.05). Eight out of 66 patients developed microalbuminuria at follow-up. Urinary albumin excretion at follow-up was comparable between patients with normal and abnormal post-exercise urinary albumin excretion; moreover post-exercise urinary albumin excretion was within the normal range in 5 out of 8 patients with microalbuminuria at follow-up. In conclusion post-exercise albuminuria does not seem to be a useful predictor of the onset of microalbuminuria in Type 1 diabetic children and adolescents.