‘Microalbuminuria’ in type I (insulin-dependent) diabetic patients with and without retinopathy

Summary We investigated the frequency of microalbuminuria (albumin excretion rate, AER>15 μg/min) (‘overnight’ urine collection and radioimmunological evaluation) and its relation to retinopathy (assessed by fluorangiography) in 113 type I (insulin-dependent) diabetic subjects (aged 31±13 years; diabetes duration 11±7 years), all Albustix-negative. Sixty eight patients (60.2%) were free of retinal lesions, 31 (27.4%) had background retinopathy and 14 (12.4%) had proliferative retinopathy. Microalbuminuria was found in 25 patients (22%). Fifteen patients (13%) showed both retinopathy and microalbuminuria. Fifteen % (10/68) of the patients with no retinopathy and sixteen % (5/31) of those with background retinal lesions had microalbuminuria, while 29% (4/14) of the patients with proliferative retinopathy were normoalbuminuric. Among the 29 patients with diabetes for less than five years, 1 had retinopathy and 4 had microalbuminuria. Out of 15 patients with both retinopathy and microalbuminuria, 13 (87%) had had diabetes for more than 10 years. Diabetic retinopathy is more frequent than microalbuminuria (40vs 22%). Although the linkage between retinopathy and microalbuminuria is weak, after ten years of diabetes the two complications may frequently coincide. This work was performed within the context of theRicerca Finalizzata della Regione Toscana. In addition, it was supported in part by grant n ^o 84.02442.56 from the National Research Council and by a grant from theMinistero della Pubblica Istruzione (Ricerca Scientifica 1986).     

Spatial frequency-selective losses with pattern electroretinogram in Type 1 (insulin-dependent) diabetic patients without retinopathy

Summary Neurosensory abnormalities have been implicated in the first stages of diabetic retinopathy. The activity of retinal ganglion cells in 24 Type 1 (insulin-dependent) diabetic patients with short disease duration without retinopathy on fluorescein angiography was investigated by using a pattern electroretinogram in response to sinusoidal gratings of different spatial frequencies (0.6, 1.0, 1.4, 2.2, 4.8 cycles/deg), counterphase modulated at 8 Hz. The pattern electroretinogram reflects, at least in part, the activity of subsets of generators (i. e., ganglion cells) which show spatial selectivity. Mean pattern electroretinogram amplitude was significantly reduced in patients at lower and intermediate, but not at higher spatial frequencies compared with 40 agematched control subjects. At 1.4 cycles/deg the pattern electroretinogram amplitude was significantly correlated (r=0.59) with age at onset (p=0.002) and duration of disease (p=0.002). Our results suggest that in Type 1 diabetic patients without retinopathy, there is an early sensory deficit of specific inner retina neurons which respond preferentially to gratings of medium and large size.     

Residual B-cell function in insulin-dependent (type I) diabetics with and without retinopathy

Summary In order to evaluate if residual B-cell function is a protecting factor against the development of diabetic retinopathy in type I diabetics we measured C-peptide levels before and after glucagon stimulation (1 mg i.v.) in 74 type I diabetics. In all patients retinopathy was assessed by fluorescein angiography and retinal lesions were classified as: grade 0, normal; grade 1, background retinopathy; grade 2, proliferative retinopathy. We then correlated the degree of retinopathy to sex, age, duration of diabetes, smoking, percentage of ideal body weight, systolic and diastolic blood pressure, serum cholesterol, triglycerides, creatinine and C-peptide by means of multiple linear regression analysis. Twenty-three out of 74 type I diabetics had retinopathy. In all 7 subjects with proliferative retinopathy duration of diabetes exceeded 10 years. There was significant correlation between retinopathy and duration of diabetes (r=0.373, p<0.001). No correlation was found between retinopathy and all the other variables, in particular between retinopathy and basal C-peptide or C-peptide increment (Δ). An inverse correlation was found between the increment of C-peptide and duration of diabetes (r=−0.404, p<0.01). Our data show that residual B-cell function cannot be considered a protecting factor against the development of diabetic retinopathy.     

Lipoprotein compositional abnormalities in type 1 (insulin-dependent) diabetic patients

Patients with type 1 (insulin-dependent) diabetes mellitus in good metabolic control usually have normal plasma lipid levels yet they have an increased incidence of vascular complications. Abnormalities in the distribution and composition of lipoprotein subfractions might in part be responsible for the macroangiopathy seen in type 1 diabetes mellitus. The plasma lipids, lipoproteins and apolipoproteins were studied in 9 type 1 diabetic patients during conventional insulin therapy and in 14 healthy controls. Plasma lipoproteins were analysed by ultracentrifugation in a zonal rotor to evaluate their concentrations and flotation properties and for compositional analysis. In diabetic patients the mean glycosylated haemoglobin (HbA_1c) was 9.44±1.02% and the plasma lipid concentrations were not significantly different from healthy controls. The very low density lipoprotein (VLDL) subclass cholesterol concentrations were no different in diabetic patients and control subjects, but the VLDL cholesterol/triglyceride ratio was significantly lower in diabetic patients than in control subjects (0.34±0.05 vs 0.85±0.14; p<0.05). The flotation rate of LDL₂, the major component of low density lipoprotein (LDL) was lower in the diabetic patients compared with the control subjects. The cholesterol concentrations of intermediate density lipoprotein and LDL₃, the minor component of LDL, were significantly higher (0.17±0.03 and 0.83±0.14 mmol/l respectively) in diabetic patients than in control subjects (0.05±0.02 and 0.24±0.08 mmol/l). The flotation properties and cholesterol concentrations of the high density lipoprotein (HDL) subclass, and the protein-lipid composition of LDL₂, HDL₂ and HDL₃, were no different in diabetic patients and control subjects. Diabetic patients had lower apoprotein AII and higher CII and E levels than control subjects. the plasma lipoproteins in type 1 diabetes mellitus are characterized by increased intermediate density lipoprotein and LDL₃ concentrations and by abnormal LDL₂ flotation properties. These lipoprotein abnormalities might have a role in atherogenesis in type 1 diabetic patients since similar alterations were associated in some recent epidemiological studies with an increased incidence of cardiovascular disease in non-diabetic patients.     

血清视黄醇结合蛋白4在2型糖尿病视网膜病中的价值

目的 通过测定正常糖调节者、合并与未合并糖尿病视网膜病(DR)的2型糖尿病(T2DM)患者血清视黄醇结合蛋白4(RBP4)浓度以及视黄醇结合蛋白4/甲状腺素转运蛋白(RBP4/TTR)比值探讨RBP4在DR中的意义.方法 选取2008年1月至9月苏州大学附属第一医院内分泌科收治的72例2型糖尿病住院患者,应用酶联免疫法和全自动生化分析仪检测35例合并DR的T2DM患者(DR组)血清RBP4、TTR、真胰岛素、C肽、糖化血红蛋白等,并与37例非DR的2型糖尿病患者(NDR组)和30名正常糖调节者(NGR组)作横断面对照.所有入选对象均符合以下标准:(1)排除肝肾疾病,并且入院后生化检查无肝酶、胆红素、白蛋白及球蛋白异常;尿蛋白/尿肌酐＜0.2,肾小球滤过率＞90 ml/min;(2)无营养不良及体重指数(BMI)＜19 kg/m2;(3)无感染及应激状态,且血清超敏C反应蛋白＜3.0 mg/L;(4)1个月内未服用维生素A、铁剂及影响其代谢的药物.采用方差分析、t检验、二元Logistic回归等进行统计学分析.结果 DR组RBP4/TTR较NDR组及NGR组显著增高(0.12±0.06、0.09±0.04、0.072±0.021,F=9.562,P＜0.05).DR组RBP4与NGR组比较差异有统计学意义[(16±4)、(13±3)mg/L,t=3.74,P＜0.05],但与NDR组无统计学差异[(15±4)、(15±3)mg/L,t=1.73,P＞0.05].分别将RBP4和RBP4/TTR引入二元Logistic回归分析,发现RBP4(B=0.214,OR=1.239,P＜0.05)和RBP4/TTR(B=0.718,OR=2.051,P＜0.05)均为DR的危险因素.结论 血清RBP4可能在T2DM发生DR的过程中起作用;血清RBP4/TTR比值在评估DR危险因素时的价值要优于血清RBP4浓度.     

Ophthalmological follow-up of Type 1 (insulin-dependent) diabetic patients after kidney and pancreas transplantation

We studied the effect of successful kidney and pancreas transplantation on visual function and diabetic retinopathy in 18 patients with long-term Type 1 (insulin-dependent) diabetes mellitus (17 to 38 years) and with advanced proliferative retinopathy. The average age of the patients was 42 years. Prior to transplantation, 5 eyes were in end-stage ophthalmic complication due to neovascular glaucoma. An ophthalmological follow-up was performed between 1–6 years post-surgery. Analysis of the results showed that the diabetic retinopathy had stabilized after transplantation in 12 cases (66 %) with a supplementary photocoagulation in the majority of cases. The proliferation continued in 4 patients (22 %) leading to blindness in 2 patients and recurrence of vitreous haemorrhages despite the photocoagulation in the other 2 cases. An improvement was observed on fluorescein angiography in a patient with pre-papillar glial proliferation without photocoagulation. Ten patients were reported to have a cataract and were operated on in two cases before transplantation; in one patient, the cataract increased following transplantation. In conclusion, the kidney and pancreas transplantation was not effective in our patients in reversing the clinical and angiographic signs of diabetic retinopathy. Moreover, a worsening of the lesions was observed in some cases; this was probably due to the irreversible microangiopathic lesions due to advanced evolution of diabetes.     

Retinal haemodynamics in individuals with well-controlled type 1 diabetes

Aims/hypothesis Abnormalities in retinal haemodynamics have been reported in patients with type 1 diabetes in advance of clinical retinopathy. These abnormalities could therefore be useful as early markers or surrogate endpoints for studying the microangiopathy. Since the DCCT, the increased focus on good glycaemic control is changing the natural history of diabetic retinopathy. Based on this, the aim of this study was to investigate whether patients with type 1 diabetes treated entirely or mostly in the post-DCCT era and tested in the absence of confounding factors show retinal haemodynamic abnormalities. Methods We measured retinal haemodynamics by laser Doppler flowmetry in 33 type 1 diabetic individuals with no or minimal retinopathy (age 30 ± 7 years, duration of diabetes 8.8 ± 4.6 years, 9% showing microaneurysms), and 31 age- and sex-matched non-diabetic controls. The study participants were not taking vasoactive medications, and blood glucose at the time of haemodynamic measurements was required to be between 3.8 and 11.1 mmol/l. Results HbA_1c was 7.5 ± 1.2% and blood glucose 7.7 ± 2.8 mmol/l in these type 1 diabetic individuals, indicating relatively good glycaemic control. Retinal blood speed, arterial diameter and blood flow were not different between the diabetic individuals and the matched controls. Conclusions/interpretation Type 1 diabetic patients with no or minimal retinopathy who maintain relatively good glycaemic control do not show abnormalities of the retinal circulation at steady state, even after several years of diabetes. In such patients it may be necessary to test the vascular response to challenges to uncover any subtle abnormalities of the retinal vessels.     

Urinary growth hormone excretion during puberty in type 1 (insulin-dependent) diabetes mellitus

The excretion of urinary growth hormone was measured by a highly sensitive direct immunoradiometric assay in a cross-sectional study during puberty in 70 children with Type 1 (insulin-dependent) diabetes mellitus and 94 normal children. In normal children (n = 24) and diabetic children (n = 17) overnight urinary growth hormone excretion correlated significantly with the mean overnight plasma concentration (r = 0.70, p less than 0.001, and r = 0.70, p less than 0.001), indicating that urinary GH excretion reflects the circulating endogenous GH level. Overnight urinary growth hormone excretion increased during puberty. In normal and in diabetic children there was a peak in boys at genital stage 4 (both p less than 0.01), and in girls at breast stage 2 (both p less than 0.02). The diabetic children excreted more urinary growth hormone than the normal children at every pubertal stage. Excretion of albumin, retinol binding protein and N-acetyl-beta-D-glucosaminidase was measured in urine from 38 diabetic children. Urinary growth hormone correlated weakly with urinary albumin (r = 0.49, p less than 0.01), retinol binding protein (r = 0.42, p less than 0.01), and N-acetyl-beta-D-glucosaminidase (r = 0.43, p less than 0.01). Urinary GH excretion was not related to blood glucose control (HbA1) in boys (n = 31) or girls (n = 39). The measurement of urinary growth hormone provides an assessment of endogenous growth hormone during puberty in normal and diabetic children. However, caution must be exercised in interpreting urinary growth hormone data from diabetic patients with increased excretion of albumin and retinol binding protein.     

Urinary excretion of retinol-binding protein in type 1 (insulin-dependent) diabetic patients with microalbuminuria and clinical diabetic nephropathy

The urinary excretion of retinol-binding protein (RBP) was studied in 101 insulin-dependent diabetic patients allocated to three groups according to 24-h urinary albumin excretion rate (UAE) (median of three urine collections): group 1 (n=45), normal UAE<30 mg/24h; group 2 (n=27), microalbuminuria (UAE 30–300 mg/24 h); and group 3 (n=29), clinical diabetic nephropathy (UAE>300 mg/24 h). We used 23 healthy subjects as controls. Fractional clearance of RBP (FC-RBP) and its 24-h urinary excretion rate (URBP) were higher in each diabetic group than in healthy subjects, the highest values being found in group 3. Groups 1 and 2 did not differ in URBP and FC-RBP. There was a correlation between FC-RBP and haemoglobin A1c in both the total diabetic cohort (P<0.001) and in diabetic patients in groups 1 and 2 with a glomerular filtration rate of more than 90 ml/min (P<0.05). No correlation was found between FC-RBP and UAE and/or duration of diabetes in any of the diabetic groups. We conclude that the increased urinary excretion of RBP, indicating proximal tubular dysfunction, is already present in normoalbuminuric insulindependent diabetic patients and correlates with metabolic control. Further deterioration in proximal tubular function was not observed in microalbuminuric patients, but is a late event in clinical diabetic nephropathy.     

Glycosylation of glomerular basement membrane in type 1 (insulin-dependent) diabetic children

Summary Immunoelectrophoresis of glomerular basement membrane antigens in the urine of 20 Type 1 (insulin-dependent) diabetic and 10 healthy children was performed. In 10 of the diabetic children, there was altered -1-mobility, while the other diabetic and normal children showed -2-mobility. After incubation with glucose, glomerular basement membrane antigens in the urine of healthy children showed -1-mobility. Isolated human kidney glomerular basement membrane split products obtained by proteolytic degradation (papain, trypsin, chymotrypsin) were also investigated by immunoelectrophoresis. A difference was observed in the immunoelectrophoretic pattern of native and glycosylated glomerular basement membrane split products. A distinct increase of thiobarbituric acid assay positive glomerular basement membrane structures after incubation with glucose provides suggestive evidence for the occurrence of non-enzymatic glycosylation of glomerular basement membrane proteins. Glycosylated glomerular basement membrane proteins may contribute to both functional and morphological changes in diabetic glomerulosclerosis.     

格列齐特对糖尿病微血管病变的影响--多中心3年前瞻性研究

目的 在2型糖尿病的治疗中,评价格列齐特（商品名达美康）是否能有效地防止微血管病变的进展。方法 7个中心为期3年的随机对照前瞻性研究。285例2型糖尿病分成格列齐特和格列本脲两个治疗组,调整降糖药用量、定期监测空腹及餐后2小时血糖以及糖基化血红蛋白至控制目标。每年检查眼底及尿微量白蛋白排量。结果 初访时两组患者的平均年龄、性别、糖尿病病程、血糖控制水平、血压、视网膜病变程度及尿微量白蛋白排量差异均无显著性,3年治疗中,两组的血糖控制及血压水平亦无差异。3年末格列齐特治疗组视网膜病变进展1期3有4例（2．58％）,格列本脲治疗组有24例（18．46％）,差异有显著性（P＜0．0001）。多因素Logistic逐步回归分析显示格列齐特治疗与视网膜病变进展1期呈独立负相关关系（P＝0．0001）。利用相同的分析模式,3年末格列齐特治疗与尿微量白蛋白排量增加≥20μg/min状态也呈独立负相关关系（P＝0．0096）。结论在本研究人群,格列齐特治疗3年防止视网膜病变进展1期和尿微量白蛋白轻度进展的作用稍优于格列本脲。     

Early glomerulopathy is present in young,Type 1 (insulin-dependent) diabetic patients with microalbuminuria

Summary Increased urinary albumin excretion, microalbuminuria, may be the first sign of early diabetic nephropathy. We examined glomeruli by morphometric methods in 17 patients with Type 1 (insulin-dependent) diabetes mellitus and microalbuminuria. The median age was 19 (range 18–29) years, duration of diabetes 12 (8–15) years, mean blood pressure 93 (87–115) mm Hg, glomerular filtration rate 132 (101–209) ml·min⁻¹·1.73 m²⁻², albumin excretion rate (mean over 1 year) 32 (15–194) μg/min. Reference data were obtained from 11 healthy kidney donors. Mesangial volume estimates were obtained by serial sectioning in three total profiles in each of three glomeruli in diabetic patients. Basement membrane thickness and matrix volume fraction were estimated from one level per glomerulus. Two matrix parameters, matrix star volume and matrix thickness, were estimated. Interstitial volume fraction in cortex was measured by light microscopy. The morphological parameters were significantly increased in the diabetic group compared to the control group, basement membrane thickness (mean with 95% confidence intervals) was 595 nm (549–641 nm) vs 305 nm (287–325 nm),p=0.0001; mesangial volume fraction 0.22 (0.21–0.23) vs 0.19 (0.18–0.21),p=0.04, and matrix volume fraction 0.13 (0.12–0.13 vs 0.09 (0.08–0.10),p=0.001. Also matrix star volume and thickness, interstitial volume fraction and mean capillary diameter were significantly increased. The intra-individual variation among glomeruli expressed as coefficient of variation was 7.4% vs 9% (basement membrane thickness) and 11.7% vs 25% (mesangial volume fraction) in the diabetic and the control group, respectively. Increment of basement membrane thickness and matrix volume fraction per year were significantly correlated with mean 1-year HbA_lc (r=0.55 andr=0.51, respectively). We conclude that microalbuminuria in Type 1 diabetes is associated with increased basement membrane thickness and also mesangial matrix expansion. This increment seems to correlate with glycaemic control.     

Pericyte mitogenic activity is reduced in the blood of type 1 diabetic patients with and without retinopathy

Selective loss of capillary pericytes occurs early and specifically in diabetic retinopathy. We have investigated whether blood derivatives from patients with longterm type 1 (insulin-dependent) diabetes and no retinopathy differ from those with retinopathy and/or non-diabetic controls in their ability to stimulate DNA synthesis in cultured bovine retinal pericytes and endothelial cells. As a general trend, whole blood serum, platelet-rich plasma and platelet-free plasma from patients without and with retinopathy stimulated thymidine incorporation in both cell types less than derivatives from controls. Serum, 0.1% v/v final concentration in culture medium, from patients without retinopathy was less active (114.5±24.5% of a standard stimulus produced by 0.1% fetal calf serum) than that from patients with the complication (132.6±20.8%,P=0.003) and both were less potent than control sera (143.6±28.0%,P<0.001 andP=0.013, respectively). Lack of support from circulating factor(s) may contribute to the disappearance of pericytes from the capillary wall in diabetes but further investigations are necessary to clarify the mechanisms that prevent the development of microangiopathy in some patients.     

Pancreas transplant alone has beneficial effects on retinopathy in type 1 diabetic patients

Aims/hypothesis The effects of successful pancreas transplant alone (PTA) on chronic complications of diabetes, in particular diabetic retinopathy, remain disputed. We prospectively studied the course of diabetic retinopathy in PTA recipients and in non-transplanted (non-PTA) type 1 diabetic patients.Methods The PTA and non-PTA groups consisted respectively of 33 (follow-up: 30 ± 11 months) and 35 patients (follow-up: 28 ± 10 months). Best corrected visual acuity, slit lamp examination, intraocular pressure measurement, ophthalmoscopy, retinal photographs, and in selected cases angiography were performed. Diabetic retinopathy and its improvement/deterioration were assessed according to criteria proposed by the Eurodiab Study.Results At baseline, 9% of PTA and 6% of non-PTA patients had no diabetic retinopathy, 24 and 29% had non-proliferative diabetic retinopathy (NPDR), whereas 67 and 66% had laser-treated and/or proliferative diabetic retinopathy (LT/PDR), respectively. No new case of diabetic retinopathy occurred in either group during follow-up. In the NPDR PTA group, 50% of patients improved by one grading, and 50% showed no change. In the LT/PDR PTA, stabilisation was observed in 86% of cases, whereas worsening of retinopathy occurred in 14% of patients. In the NPDR non-PTA group, diabetic retinopathy improved in 20% of patients, remained unchanged in 10%, and worsened in the remaining 70%. In the LT/PDR non-PTA group, retinopathy did not change in 43% and deteriorated in 57% of patients. Overall, the percentage of patients with improved or stabilised diabetic retinopathy was significantly higher in the PTA group. No differences were found between the two groups with regard to cataract lesions and intraocular pressure values.Conclusions/interpretation Despite a relatively short follow-up, our study shows that successful PTA can positively affect the course of diabetic retinopathy.     

The changing epidemiology of diabetic microangiopathy in type 1 diabetes

Diabetic microvascular complications in the kidney and the eye are a major burden for diabetic patients due to increased morbidity and mortality. Furthermore, diabetic nephropathy is the leading cause of end-stage renal disease and diabetic retinopathy is the leading cause of blindness in younger patients, representing a major public health concern. During the past two decades beneficial effects of, in particular, aggressive antihypertensive control and strict glycaemic control have been demonstrated in randomised controlled clinical trials. Technological improvements in diabetes care have made good metabolic control easier to achieve. Has this led to an improved prognosis? In observational studies from dedicated centres, a decrease from 47 to 13% has been reported in the incidence of proliferative diabetic retinopathy after 20–25 years of diabetes, and the incidence of overt diabetic nephropathy after 20 years has decreased from 28 to 5.8%. Even functional and morphological remission of diabetic nephropathy has been reported. Despite this, recent population-based studies have failed to demonstrate a decrease in the incidence of blindness caused by diabetes, and the incidence of end-stage renal disease has progressively increased. This may, in part, be the result of a combination of increasing numbers of diabetic patients and a lag phase between improvement in management and a decline in end-stage complications. It is of concern, however, that the results from specialised centres may not apply to routine diabetes care. It is, therefore, mandatory that the beneficial effects of pharmacological and non-pharmacological interventions demonstrated in clinical trials and recommended by treatment guidelines are translated into clinical practice to ensure a widespread improvement in prognosis.     

Plasma lipoprotein abnormalities in type 1 (insulin-dependent) diabetes mellitus

Lipoprotein abnormalities may well contribute to the increased risk of coronary heart disease, cerebrovascular disease and peripheral vascular disease observed in type 1 (insulin-dependent) diabetes mellitus. The spectrum of diabetes-associated changes in lipoprotein metabolism is discussed. The plasma levels of lipoprotein cholesterol and triglycerides are largely influenced by the degree of glycaemic control. With poor metabolic control, plasma cholesterol and triglycerides are frequently elevated. In contrast, in well-regulated patients without micro- and macrovascular complications lipid levels are generally normal or even favourable, although lipoprotein composition abnormalities can persist despite intensified insulin treatment. With the development of diabetic nephropathy the cardiovascular risk increases markedly and this complication is associated with increased concentrations of cholesterol and of the atherogenic lipoprotein species, lipoprotein(a), and low levels of high-density lipoprotein cholesterol. The rationale for treatment of lipid disorders in diabetes mellitus is based upon results of trials conducted primarily in non-diabetic populations. It is hoped that with increased recognition of dyslipidaemia and aggressive therapeutic measures the overkill in diabetes mellitus from macrovascular diseases will be reduced.     

Increased microvascular fluid permeability in young Type 1 (insulin-dependent) diabetic patients

Summary Microvascular fluid permeability was assessed by determination of the capillary filtration coefficient in the forearm of ten young Type 1 (insulin-dependent) diabetic patients with a short duration of diabetes, satisfactory glycaemic control and minimal evidence of micro angiopathy, and ten age- and sex-matched controlsubjects. A strain gauge plethysmographic method with a computer based logging and analysis system was used. This enabled differentiation between the volume filling and fluid filtration components of the response to venous pressure elevation. The median capillary filtration coefficient was found to be significantly higher in the young diabetic patients in comparison with control subjects (9.2×10^–3 ml · min^–1 · 100 g tissue^–1 mmHg^–1 vs 3.8×10^–3ml · min^–1 · 100 g tissue^–1 · mm Hg^–1, p<0.001). There were no significant correlations between capillary filtration coefficient and either plasma glucose concentration, haemoglobin A_1c or duration of diabetes. As there is no evidence from other studies to support an increase in capillary surface area in the forearms of young Type 1 diabetic patients, these results may reflect a primary change in microvascular fluid permeability.     

Lipoprotein (a) and microvascular disease in type 1 (insulin-dependent) diabetes.

The influence of albuminuria and proliferative retinopathy on concentration of serum lipoprotein (a) was examined cross-sectionally in 90 Type 1 diabetic patients. Concentrations of lipoprotein (a) were less in those with normoalbuminuria (90 (8-882) (median (range] U l-1) than in those with micro- or macro-albuminuria (137 (19-1722) U l-1, p less than 0.05). The prevalence of patients whose lipoprotein (a) concentrations were greater than 200 U l-1 was also greater (45% vs 24%, p = 0.03) among patients with albuminuria, but no difference was found between the microalbuminuric and macroalbuminuric groups (53 and 41%, respectively), or between those with or without proliferative retinopathy. The present finding that lipoprotein (a) concentrations may be increased at an early stage of diabetic renal disease may in part account for the excess ischaemic heart disease associated with diabetic nephropathy.