The relationship between mean platelet volume with microalbuminuria and glycemic control in patients with type II diabetes mellitus

Microalbuminuria is the best predictor of diabetic nephropathy development in patients with type II diabetes mellitus (DM). It is also accepted as an indicator of diabetic microangiopathy. Increased activation of platelets has been suggested to be involved in the pathogenesis of vascular complications. In light of these findings, this study was designed to investigate the association of microalbuminuria — an indicator glycemic control and microangiopathy — with mean platelet volume (MPV). Subjects underwent laboratory analyses and their MPV, HbA1c, serum creatinine, fasting, and postprandial blood glucose levels and 24-hour urine albumin levels were recorded. All statistical analyses were performed using SPSS v13.0 for Windows XP. Mann–Whitney U-test, student's t-test, spearman correlation analysis, ROC analysis, categorical regression analysis, and chi-square test were used for statistical evaluations. The study included 354 patients with type II DM. The median MPV value of microalbuminuria-positive patients was 9 (8–9.5)?fl while MPV of patients without microalbuminuria was 8.5 (8–9.2)?fl and the difference was statistically significant (p?=?0.004). We determined positive correlation between MPV and 24-hour urine microalbuminuria (r?=?0.14, p?=?0.009). There were no significant differences between patients with HbA1c levels below and above 7% in terms of MPV (p?>?0.05). We determined no correlation between MPV and HbA1c levels (r?=??0.36, p?=?0.64). This study determined a significant positive relationship between microalbuminuria — a microvascular complication of diabetes — and MPV. No significant correlation was identified between poor glycemic control and MPV in diabetic patients. However, we are in the opinion that the association between poor glycemic control and MPV in type II diabetic patients should be investigated in prospective studies with larger samples.     

Increased prevalence of fetal haemoglobin in Type 1 (insulin-dependent) diabetes mellitus

Summary Fetal haemoglobin levels were measured in 106 patients with Type 1 (insulin-dependent) diabetes mellitus during a period of two to three years. In 15 patients (14.1%) increased fetal haemoglobin levels (>0.5%), determined by high pressure liquid chromatography, were found in contrast to 3% in a healthy control group (n: 100) of equal age distribution. In children aged over 6 years, elevated fetal haemoglobin levels were measured in 13 diabetic patients (13.3%) in contrast to none of the control group. There was no correlation between fetal haemoglobin levels and duration of diabetes, diabetic control (glycated haemoglobin) and dosage of insulin (U·kg^–1, day^–1). The 15 patients had a younger mean age at onset of diabetes (5.6 years) than a sex and age matched control group of diabetic patients without increased fetal haemoglobin levels (7.4 years, p<0.05). Longitudinal assessment revealed a significant decline of fetal haemoglobin levels with age (p<0.005) but a further increase in fetal haemoglobin levels were found in adolescent patients (n: 2). These data indicate a possible effect of insulin-treatment on delaying transition from fetal to adult haemoglobin synthesis or on reactivation of fetal haemoglobin production.     

Smoking and metabolic control in patients with insulin-dependent diabetes mellitus

Within a defined geographical area, all 192 subjects with insulin-dependent diabetes of at least 2 years duration and free of diabetic complications were identified; 60 (31%) were smokers. The prevalence of smoking increased significantly with increasing haemoglobin A1c levels (17.5% among subjects with the best metabolic control, 47.5% in those with the worst control). Smoking and non-smoking diabetic patients did not differ in attitudes towards the disease, psychological well-being, extent of tedium, frequency of self-controls of blood glucose or proportion of patients with any sick leave in the preceding 2 years. In a case referent study of 25 matched patients with good or poor metabolic control, exposure to smoking was significantly more common among those with poor control (odds ratio 6.0). Thus there are several lines of evidence that smoking is associated with impaired metabolic control in patients with diabetes.     

Serum lipids and lipoproteins in insulin-dependent diabetic patients with persistent microalbuminuria

Serum lipid and lipoprotein concentrations were measured in 18 insulin-dependent diabetic patients with persistent microalbuminuria and an equal number with persistently normal albumin excretion. The groups were matched for sex, age, duration of diabetes, body mass index, insulin dose, and glycosylated haemoglobin. Diabetic patients with persistent microalbuminuria were found to have a significantly lower high density lipoprotein (HDL) cholesterol concentration (difference 0.29, 95% Cl 0.12 to 0.46, mmol l-1, p less than 0.01) and a higher low density lipoprotein (LDL) cholesterol:HDL cholesterol ratio (difference 0.97, 95% Cl 0.29 to 1.65, p less than 0.01) than patients with normal albumin excretion. No significant differences were found in total cholesterol, triglycerides, LDL cholesterol, apolipoprotein (apo) A-I and apo B concentrations. Compared to an age and sex-matched group of non-diabetic subjects with normal albumin excretion, diabetic patients with persistent microalbuminuria had significantly higher concentrations of total cholesterol (p less than 0.05), LDL cholesterol (p less than 0.05) and apo B (p less than 0.01), but a lower concentration of HDL cholesterol (p less than 0.05). No significant differences were found in serum lipids and lipoproteins between diabetic patients with normal albumin excretion and non-diabetic subjects.     

非胰岛素依赖型糖尿病微量白蛋白尿患者红细胞膜ATPases活力的变化

测定非胰岛素依赖型糖尿病(NIDDM)微量白蛋白尿患者20例及NIDDM无微量白蛋白尿患者20例和正常人20例红细胞膜ATPases活力。结果NIDDM微量白蛋白尿患者Na~+-K+ATPase,Ca~(2+)+ATPase活力明显低于正常人(P分别<0.05及0.001),Mg~(2+)ATPase活力无明显改变(P>0.05).NIDDM无微量白蛋白尿患者Ca~(2+)ATPase活力也低于正常人(P<0.01),但不及微量白蛋白尿组明显;无白蛋白尿组Na~+-K~+ATPase活力虽有下降,但P>0.05,Mg~(2+)ATPese活力无明显变化(P>0.05).     

Association of D-dimer with microalbuminuria in patients with type 2 diabetes mellitus

Background Microalbuminuria has been reported to be related to incidence of cardiovascular complications in diabetes. No consistent findings have been obtained on the relationships of microalbuminuria with blood coagulation and fibrinolysis. The purpose of this study was to determine whether microalbuminuria is associated with blood markers reflecting coagulation and fibrinolysis activities in patients with type 2 diabetes. Methods The relationships of albumin excretion rate (AER) with atherosclerosis-related variables, including blood coagulation and fibrinolysis markers, were investigated in patients with type 2 diabetes who showed normoalbuminuria (AER: less than 20 μg/min) and microalbuminuria (AER: 20 μg/min or higher and less than 200 μg/min). Results AER was significantly correlated with body mass index (BMI), maximum intima-media thickness of common carotid arteries, blood HDL cholesterol, uric acid, creatinine and D-dimer. On the other hand, AER showed no significant correlation with blood platelets, fibrinogen, thrombin–antithrombin III complex, plasmin–α2 plasmin inhibitor complex and plasminogen activator inhibitor-1. In multiple regression analysis, using age, sex, BMI, pulse pressure, hemoglobin A1c, HDL cholesterol, uric acid, creatinine, D-dimer and history of anti-thrombotic therapy as explanatory variables, only D-dimer showed a significant correlation with AER. The mean level of log-converted D-dimer after adjustment for age and sex was significantly higher in subjects with microalbuminuria than in those with normoalbuminuria. Conclusions D-dimer is associated with microalbuminuria in patients with diabetes and this suggests that glomerular dysfunction is in part mediated by hypercoagulability.     

老年2型糖尿病患者纤维蛋白原与尿微量白蛋白的相关性研究

目的探讨老年2型糖尿病患者正常范围内血浆纤维蛋白原(FIB)与尿微量白蛋白(UMA)的相关性。方法收集2012年10月至2014年10月上海市第五人民医院收治的869例老年2型糖尿病患者的临床资料。将患者按FIB四分位数分为Q1组(<2.42 g/L)、Q2组(2.42~2.89 g/L)、Q3组(2.90~3.61 g/L)、Q4组(≥3.62 g/L),分析FIB与尿白蛋白与肌酐比值(UACR)的相关性。结果随着FIB水平升高,UACR水平显著升高(P<0.05)。Pearson相关分析显示,在男性和女性患者中FIB与年龄、糖尿病病程、肌酐和UACR均呈显著正相关(P<0.01)。多元逐步回归分析显示FIB是UACR的独立影响因素(P<0.01)。Logistic多元回归分析显示,在校正性别、年龄、糖尿病病程、体重指数(BMI)、收缩压、舒张压、空腹血糖(FPG)、HbAlC、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、肌酐、丙氨酸氨基转移酶(ALT)、吸烟史和饮酒史因素后,Q4组发生微量白蛋白尿和大量白蛋白尿的危险性分别是Q1组的4.536倍(95%CI 2.516~8.175,P<0.01)和13.314倍(95%CI 2.925~60.612,P<0.01),Q3组发生微量白蛋白尿和大量白蛋白尿的危险性分别是Q1组的2.177倍(95%CI 1.273~3.724,P<0.01)和4.098倍(95%CI 1.101~19.226,P<0.05)。以UACR 30 mg/g和300 mg/g为分界值,分别行FIB与UACR的ROC曲线所得FIB的最佳切点值分别为3.18 g/L和3.22 g/L。结论老年2型糖尿病患者血浆FIB与UMA密切相关,可能是糖尿病肾病的预测指标之一。     

Alterations in serum lipids and apolipoproteins in male Type 1 (insulin-dependent) diabetic patients with microalbuminuria

Summary The relationships between serum lipid, apolipoprotein levels and urinary albumin excretion were investigated in 20 male Type 1 (insulin-dependent) diabetic patients with microalbuminuria (overnight urinary albumin excretion between 10 and 200 g/min), in 18 male Type 1 diabetic patients without microalbuminuria and in 18 male control subjects. In the microalbuminuric patients low density lipoprotein cholesterol was higher than in the control subjects (p<0.05); the high density lipoprotein/low density lipoprotein cholesterol ratio was lower than in the normoalbuminuric diabetic patients (p<0.05), and in the control subjects (p<0.01); apolipoprotein B was higher than in the normoalbuminuric patients (p<0.05); the apolipoprotein A₁/B ratio was lower than in the normoalbuminuric diabetic patients (p<0.05). Serum triglyceride was higher in the microalbuminuric diabetic patients and in the control subjects than in the normoalbuminuric diabetic patients (p<0.05, for both), but was not different between the microalbuminuric diabetic patients and the control subjects. No significant differences between the 3 groups were present with respect to serum cholesterol, high density lipoprotein cholesterol and apolipoprotein A₁. In the 2 combined Type 1 diabetic groups there were significant correlations between urinary albumin excretion and the high density lipoprotein/low density lipoprotein cholesterol ratio (R -0.40, p<0.02), apolipoprotein B (R0.35, p<0.05) and the apolipoprotein A₁/B ratio (R -0.44, p<0.01). These results indicate microalbuminuria related differences in lipid and apolipoprotein levels in male Type 1 diabetic patients, which may contribute to an increased risk of cardiovascular disease.     

Prevalence of microalbuminuria in children with Type 1 (insulin-dependent) diabetes mellitus

Summary The prevalence of microalbuminuria was determined in children aged 7 to 18 years with Type 1 (insulin-dependent) diabetes of more than 2 years' duration. All patients (n =102) attending 2 diabetes clinics were asked to collect 2 overnight timed urine samples for albumin analysis by radioimmunoassay. Complete urine collection was obtained in 97 patients (95%). Overnight urinary albumin excretion rates were also measured in 36 healthy children matched for age and sex. Nineteen of the 97 patients (20%) had microalbuminuria, i. e. overnight urinary albumin excretion rates above the upper normal level (14 g/min) in both urine collections. Microalbuminuria was only demonstrated in patients aged 15 years, prevalence 37% (19/52 patients). Arterial blood pressure was elevated, mean 122/84±11/9mmHg, in the microalbuminuric group (19 patients) compared to the age-matched normoalbuminuric diabetic group (33 patients), mean 117/74±10/10 mm Hg,p < 0.001. The prevalence of simplex retinopathy was identical in these two groups, i. e. 25%. Glycosylated haemoglobin was slightly higher in the microalbuminuric patients,p < 0.10. Our cross-sectional study reveals a high prevalence (37%) of persistent microalbuminuria, a stage highly predictive of later development of diabetic nephropathy, in Type 1 diabetic children aged 15 years.     

Predictors of the development of microalbuminuria in patients with Type 1 diabetes mellitus: a seven-year prospective study

Aims To determine risk factors for the development of persistent microalbuminuria (albumin excretion rate (AER) ≥ 30 μg/min) in Type 1 diabetes mellitus. Methods One hundred and forty-eight initially normotensive Type 1 diabetic patients with normal albumin excretion (< 30 μg/min) were followed prospectively in hospital diabetes outpatient clinics for a median of 7 years. Main outcome measures were: progression to persistent microalbuminuria (albumin excretion rate ≥ 30 μg/min on at least two consecutive occasions); rate of change of albumin excretion rate; development of arterial hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg or commencement of antihypertensive therapy). Results In a median follow-up period of 7 years (range 6 months to 8 years), 14 patients progressed to persistent microalbuminuria, a cumulative incidence of 11% (95% confidence interval 6.36–16.94). AER remained persistently < 30 μg/min in 109 subjects and 25 developed intermittent microalbuminuria. In those who developed persistent microalbuminuria, baseline AER (16.2 (13.9–19.1) vs. 5.2 (3.8–9.2) μg/min, P < 0.01), blood pressure (136 (123–148)/80 (74–85) vs. 121 (118–124)/72 (70–73) mmHg, P < 0.05), and HbA₁ (10.2 (9.1–11.4) vs. 9.0 (8.7–9.4)%, P < 0.05) were higher than in those who continued to have persistent normoalbuminuria, retinopathy was more severe and height (1.64 (1.57–1.71) vs. 1.70 (1.69–1.72) m, P < 0.05) less. In multivariate analysis, baseline AER was the strongest predictor of the development of persistent microalbuminuria (P < 0.0001), followed by mean arterial pressure (P = 0.02) and HbA₁ (P = 0.05). Conclusions The level of AER, raised blood pressure and poor glycaemic control are the most important predictors of the development of microalbuminuria in Type 1 diabetes.     

Kidney function and glomerulopathy over 8 years in young patients with Type I (insulin-dependent) diabetes mellitus and microalbuminuria

Aims/hypothesis: We aimed to investigate prospectively the interrelation between kidney function and glomerular morphological changes over 8 years in young patients with Type I (insulin-dependent) diabetes mellitus and microalbuminuria. Methods: Kidney biopsies were taken at baseline and after 8 years in 18 subjects who were 20 years of age (19–29 mean and range), had duration of diabetes for 11 years (7–18), and who had an albumin excretion rate of 45 μg/min (15–194). The glomerular ultrastructural parameters were analysed using stereological methods. Results: At the end of the study three patients had an increased albumin excretion rate of more than 25 % a year, two of whom developed overt nephropathy. Glomerular filtration rate declined 2.3 ml/min · 1.73 m^–2· yr^–1. Glomerular volume, volume fractions of matrix and mesangium, and basement membrane thickness showed an increase over the 8 years. Multiple regression analysis showed that mean 8-years HbA_{1 c}, matrix volume fraction_baseline and basement membrane thickness BMT_baseline accounted for 70 % of the variation in AER at the end of the study. Mesangial volume fraction_baseline, glomerular filtration fraction_baseline, and mean 8-year HbA_{1 c} accounted for 73 % of the change in glomerular filtration rate from baseline. Smoking was strongly associated with the glomerular filtration rate at baseline (r = 0.65). When glomerular filtration rate_baseline was omitted from the equation, smoking was the only significant parameter linked to the change in glomerular filtration rate from the baseline. Conclusion/interpretation: In patients who had diabetes for 20 years, long-term hyperglycaemia and glomerulopathy found 8 years prior to the study, and possibly smoking, affected renal function (i. e. albumin excretion rate and glomerular filtration rate). [Diabetologia (2002) 45: 253–261] Received: 16 July 2001 and in revised form: 18 October 2001     

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     

Comparison of fructosamine and glycated haemoglobin in children with Type 1 (insulin-dependent) diabetes mellitus

Summary In six children (age: mean 8.4 years, range 2.2–12.6 years) with newly diagnosed Type 1 (insulin-dependent) diabetes mellitus, plasma fructosamine and glycated haemoglobin (HbA₁) were compared in respect to their disappearance during the first month after diagnosis during well controlled glycaemia. The disappearance of the surplus plasma fructosamine and HbA₁ was calculated applying exponential equations. The estimated half-lives of fructosamine (mean 57.2 days, range 40.7–77 days) and HbA₁ (mean 59.7 days, range 43.3–82 days) were not significantly different, a finding which is left unexplained.     

Paternal phenotype is associated with microalbuminuria in young adults with Type 1 diabetes mellitus of short duration.

AIMS: Susceptibility to diabetic nephropathy has not yet been causally linked to any genetic factors. We investigated in nuclear families whether parental ambulatory blood pressure, lipids and urine albumin excretion were early markers of risk of microalbuminuria in young adults with Type 1 diabetes. SUBJECTS AND METHODS: A subset of 98 young adults from the Oxford Regional Prospective Study were followed from diagnosis until aged >or= 16 years and duration of diabetes >or= 5 years (probands). Of these subjects, 24 developed microalbuminuria (males >or= 3.5 mg/mmol; females >or= 4 mg/mmol) and were designated cases, whereas 74 were controls. Family medical history, 24-h ambulatory blood pressure, urine albumin to creatinine ratio (ACR), non-fasting lipid profile and apolipoproteins (A1 and B) were measured in mothers and fathers. RESULTS: The prevalence of a parental hypertension (taking anti-hypertensive medication or daytime blood pressure > 140/90 mmHg), was similar in cases and controls (29% vs. 35%; chi2 test, P = 0.3). The systolic blood pressure night to day ratio and also ACR were higher in the fathers of cases when compared with the fathers of controls [systolic 0.88 (0.08), n = 14 vs. 0.85 (0.12), n = 53, P = 0.041]; [ACR median (IQ range) 0.6 mg/mmol (0.2-16.9) vs. 0.47 mg/mmol (0.3-3.7), P = 0.049]. Paternal night-time systolic blood pressure, night to day systolic blood pressure ratio and ACR were correlated with an index of susceptibility to albuminuria (r = 0.25, P = 0.042, n = 69 and r = 0.28, P = 0.022, n = 0.67 and r = 0.24, P = 0.029, n = 0.85, respectively). CONCLUSIONS: Higher paternal ACR and night to day ratio of ambulatory blood pressure, but not parental hypertension or maternal factors, are associated with microalbuminuria in young adults with Type 1 diabetes.     

Prorenin and renal function in NIDDM patients with normo- and microalbuminuria

Abstract. Objectives . To assess whether prorenin is elevated and perhaps a predictor of deteriorations in albuminuria and/or renal function in NIDDM patients with normo- and microalbuminuria. Design . A cross-sectional and a longitudinal study. Setting . Outpatient diabetic clinic. Subjects . Twenty-eight NIDDM patients (16 with normoalbuminuria, 12 with microalbuminuric) and 16 healthy subjects, matched for sex, age and BMI. Fifteen patients were reinvestigated after (mean [range]) 3.1 (2.1–4.3) years. Main outcome measures . Serum prorenin and renin, urinary albumin excretion rate, and glomerular filtration rate. Results . Serum prorenin was similar in both normoalbuminuric (116 × / ÷ 1.9 μU ml^-1(geometric mean × / ÷ antilog SD) and microalbuminuric (124 × / ÷ 1.7 μU ml^-1) as well as in healthy control subjects (90 × / ÷ 1.7 μU ml^-1). Prorenin did not correlate to either urinary albumin excretion rate or glomerular filtration rate. No difference between baseline and follow-up levels of albuminuria, glomerular filtration rate or prorenin were observed. The annual changes in albuminuria, glomerular filtration rate and prorenin were not correlated, and no correlation was found between baseline prorenin levels and annual changes in albuminuria or glomerular filtration rate. Conclusions . Serum prorenin levels are not elevated in either normoalbuminuric or microalbuminuric NIDDM patients, and serum prorenin is not a valid predictor of long-term changes in albuminuria in this patient group.     

Effects of high-dose vitamin E supplementation on oxidative stress and microalbuminuria in young adult patients with childhood onset type 1 diabetes mellitus

INTRODUCTION: The aim of this study was to evaluate the effects of high-dose vitamin E supplementation (1200 mg/day) on reducing both microalbuminuria (MA) and oxidative stress in patients with type 1 diabetes mellitus (T1DM) and persistent MA. METHODS: We performed a 12-month, randomized, placebo-controlled, double-blind cross-over trial in ten Caucasian young adults (7m/3f; mean age 18.87 +/- 2.91 years) with T1DM and persistent MA.At baseline and at end of the treatment period, determination of albumin excretion rate (AER) and HbA(1c) and evaluation of the oxidant/antioxidant status were performed. RESULTS: At the beginning of the study, AER and HbA(1c) were not significantly different between the vitamin E and placebo group. No differences in terms of oxidant and antioxidant status were found between the two groups. This was associated with no significantly different urinary VEGF and TGF-beta levels. After 6 months, no significant differences in AER were observed between the two groups (p = 0.59). However, plasma and LDL-vitamin E content were significantly higher in the vitamin E group compared to the placebo group (p = 0.0001 and p = 0.004, respectively). This was associated with a significantly longer lag phase (p = 0.002) and lower MDA (p = 0.049). However, no statistically significant differences were detected in terms of VEGF and TGF-beta urinary levels. CONCLUSION: These data demonstrate that high-dose vitamin E supplementation reduces markers of oxidative stress and improves antioxidant defence in young patients with T1DM. However, although it positively affects the oxidant/antioxidant status, vitamin E supplementation does not reduce AER in patients with T1DM and persistent MA.     

Glycosylated haemoglobin in children with insulin-dependent diabetes mellitus

Summary Glycosylated haemoglobin (HbA₁) was measured serially by microcolumn chromatography in 38 children with newly diagnosed insulin-dependent diabetes. Initial HbA₁ levels of 13.6±0.5% fell significantly from day 0 (prior to therapy) both to day 1 (1.6±0.2% decrease) and to day 3–5 (2.6±0.4% decrease) (p < 0.001). This drop correlated closely with changes in blood glucose (p < 0.001), less closely and inversely with plasma bicarbonate levels (p < 0.01), but not with prior duration of symptoms or changes in serum cholesterol and triglyceride concentrations. HbA₁ levels reached a nadir of 8.2±0.3% 3 weeks to 6 months after diagnosis, and correlated with decreasing insulin dosage (p < 0.001). HbA₁ levels rose again to 11.4±0.5% in 21 patients followed for more than 3–6 months. Our results indicate that (1) HbA₁ levels change rapidly during initial stabilization of insulin-dependent diabetes suggesting that glycosylation may not be entirely irreversible, and (2) HbA₁ levels are consistent with clinical assessment of control during remission and postremission phases.     

Atrial natriuretic peptide increases urinary albumin excretion in men with Type 1 diabetes mellitus and established microalbuminuria

Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mellitus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose was maintained between 4 and 7 mmol l⁻¹ in all subjects for the duration of studies; after euglycaemia had been established, a standard oral water load (20 ml kg⁻¹ plus replacement of urinary losses) was given. Once steady state diuresis was attained, subjects received intravenous infusion of either placebo (0.9 % saline), low dose (2.5 pmol kg⁻¹ min⁻¹) or high dose (5.0 pmol kg⁻¹ kg min⁻¹) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-dependent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) μg min⁻¹; low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) μg min⁻¹, p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) μg min⁻¹, p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all studies. We conclude that intravenous infusions of ANP cause a dose-dependent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM. © 1998 John Wiley & Sons, Ltd.