Influence of pregnancy on long-term progression of retinopathy in patients with type 1 diabetes

Aims/hypothesis Pregnancy in type 1 diabetic women is associated with risk of worsening of retinopathy. It has been reported that deterioration continues in the months after delivery, but direct data are lacking. It is also unclear what impact pregnancy has on the long-term progression of retinopathy. Methods We studied 59 women with type 1 diabetes who had retinal photographs before pregnancy and yearly for 5 years post pregnancy. These photographs were graded using the EURODIAB retinopathy grading system. Results The mean duration of diabetes was 14.4 ± 8.2 years and mean age at pregnancy was 29.8 ± 5.5 years. Mean HbA_1c was 8.2 ± 2.0% before pregnancy with tighter control during pregnancy itself. This value was high despite efforts to improve take-up of pre-conception care. Mean HbA_1c was 8.6 ± 1.5 during the follow-up period. At baseline, 43 (72.9%) women were free of retinopathy, 15 had non-proliferative retinopathy and one woman had previously had laser therapy. During pregnancy four women required laser therapy. Over the next 5 years none required laser therapy, although retinopathy worsened in 14 women. Ten-year follow-up data were available on 22 women, one of whom required laser therapy 8 years after pregnancy. Baseline retinopathy status was the only independent risk factor which predicted progression of retinopathy. Conclusions/interpretation Pregnancy is not associated with post-partum worsening of 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.     

2型糖尿病患者视网膜厚度的检测及其临床意义

目的　探讨 2型糖尿病患者黄斑区中心凹视网膜厚度的变化。方法　用光学相干断层扫描成像仪对 3 6例 2型糖尿病病人和 16例正常人 (对照组 )进行视网膜厚度的测量 ,同时检查眼底。根据视网膜病变的程度将 3 6例糖尿病患者分为三组 :正常视网膜组 (NR组 )、背景性视网膜病变组 (BR组 )、增殖性视网膜病变组 (PR组 )。结果　对照组黄斑区中心凹视网膜厚度为 (168± 18) μm ,糖尿病患者黄斑区中心凹视网膜厚度较正常人显著增高 (P <0 .0 5或P <0 .0 1) ,NR组视网膜厚度为 (2 0 5± 3 5 ) μm ,BR组视网膜厚度为 (2 77± 69) μm ,PR组视网膜厚度为 (3 5 4± 3 3 ) μm。结论　 2型糖尿病患者黄斑区中心凹视网膜厚度随视网膜病变程度的加重而显著增加     

Effect of metformin and insulin combination on monocyte chemoattractant protein-1 and cathepsin-D in type 2 diabetes mellitus

Background and aimsMonocyte chemoattractant protein-1 (MCP-1) and cathepsin-D are progressively raised in type 2 diabetes mellitus (T2DM) with both non proliferative and proliferative retinal disease. This study aimed to evaluate the effect of antidiabetic medications on MCP-1 and cathepsin-D.Methods60 patients of T2DM without retinopathy and 60 of diabetic retinopathy were enrolled to receive metformin (500 mg–1000 mg) combined with either glimepiride (1 mg–2 mg) or insulin. The effect of antidiabetic medications on serum MCP-1 and cathepsin-D was assessed.ResultsMean MCP-1 (pg/ml) and cathepsin-D (ng/ml) levels were significantly lower in patients of T2DM with and without retinopathy treated with metformin + insulin (468.52 ± 272.84 vs 234.30 ± 180.58; p < 0.01 and 460.15 ± 128.52 vs 517.33 ± 213.49; p = 0.214) as compared to patients treated with metformin + glimepiride (1434.02 ± 105.27 vs 1256.27 ± 76.76; p < 0.01 and 1689.36 ± 752.57 vs 919.69 ± 675.05; p = < 0.01). No significant correlation of MCP-1 and cathepsin-D with HbA1c, fasting and post prandial blood glucose were found.ConclusionPatients treated with metformin and insulin combination had lower serum MCP-1 and cathepsin-D levels which suggests that this combination may be more effective in reducing the progression of diabetic retinopathy. (CTRI/2018/05/013601).     

2型糖尿病尿白蛋白排泄和视网膜病变相互关系研究

目的了解老年２型糖尿病（２ＤＭ）患者尿白蛋白排泄（ＵＡＥ）与视网膜病变（ＤＲ）之间的关系。方法对２４３例老年２ＤＭ患者同时进行了２４ｈＵＡＥ测定、眼底检查和详细的临床资料分析。结果①ＤＲ的发生率随ＵＡＥ的增加而增加,正常、微量和大量白蛋白尿患者,ＤＲ的发生率分别为１１７％、７６０％和８３３％,增殖性ＤＲ发生率分别为１８％、１４７％和３６７％;同样,白蛋白尿的发生率亦随ＤＲ的出现和进展而明显增高;②有白蛋白尿,但不伴ＤＲ的患者,其白蛋白尿常由其他非糖尿病性疾病所致。结论老年２ＤＭ患者ＵＡＥ与ＤＲ的发生密切相关,ＤＲ的存在与否对其白蛋白尿的病因有重要提示价值。     

The effect of low-dose dopamine on renal haemodynamics in patients with type 1 (insulin-dependent) diabetes does not differ from normal individuals

Summary It is well known that patients with Type 1 (insulin-dependent) diabetes exhibit both increased glomerular filtration rate and effective renal plasma flow, which can be found even when these patients are well controlled. Usually this is attributed to a decrease in renal vascular resistance and/or to enlarged kidney size and glomerular volume. Among the factors which govern glomerular filtration rate, renal plasma flow is most important. Renal plasma flow increases if renal vascular resistance decreases. The latter might exist in insulin-dependent diabetes mellitus because of either a predominantly afferent or a predominantly efferent vasodilatation. Dopamine is an agent which causes predominantly efferent vasodilatation. Therefore, the effects of infusing a low dose of dopamine on glomerular filtration rate and effective renal plasma flow in 12 well-controlled patients with Type I (insulin-dependent) diabetes and 28 healthy volunteers were compared to investigate whether the increased glomerular filtration rate in Type 1 diabetes is caused by an efferent vasodilatation. The median increase in glomerular filtration rate during dopamine infusion amounted to 13.0% in diabetic patients and 12.5% in healthy control subjects (n. s.). It is concluded that the elevated glomerular filtration rate in well-controlled Type 1 diabetes is not caused by a predominantly efferent vasodilatation.     

Increased plasma adiponectin concentrations are associated with microangiopathy in type 1 diabetic subjects

Aims/hypothesis Insulin resistance is related to an increased risk of diabetic retinopathy and nephropathy in type 1 diabetes. Patients with insulin resistance and/or macrovascular disease have abnormally low levels of adiponectin. The aim of this study was to investigate the relationships between adiponectin and renal and retinal diabetic complications in type 1 diabetic patients.Methods In this 6-year prospective follow-up observational study, we evaluated the severity of retinopathy at baseline and determined the incident risk of microalbuminuria in 126 normoalbuminuric patients with type 1 diabetes. Each patient was age- and sex-matched to two non-diabetic control subjects.Results Plasma adiponectin concentrations were significantly higher in diabetic subjects than in control subjects (p<0.0001). The adiponectin concentration was significantly higher in patients with severe diabetic retinopathy than in those without (39.1±14.0 vs 29.0±13.0 g/ml, p=0.0005). The 18 patients who developed persistent microalbuminuria had higher adiponectin concentrations than the other patients (35.8±14.5 vs 30.6±13.7 g/ml). Increased adiponectin concentrations were independently associated with the occurrence of microalbuminuria (p=0.0158) after adjustment for baseline urinary albumin concentration (p=0.004), sex (p=0.0054), blood pressure (NS) and metabolic control (NS).Conclusions/interpretation The elevated adiponectin concentrations observed in subjects with microvascular disease may indicate an altered regulation of this adipocytokine in patients with complications associated with type 1 diabetes.     

血清对氧磷酯酶活性变化与糖尿病视网膜病变的关系

目的 探讨对氧磷酯酶(PON)活性变化与2型糖尿病视网膜病变(DR)的关系。方法 用分光光度法检测96例DR患者、82例单纯2型糖尿病(DM)患者及58例正常对照者血清PON的活性；用放免法检测血清免疫反应性胰岛素(IRI)、C肽(C—P)的水平。结果 (1)DR患者血清PON活性明显低于DM患者(F＝11．04，P＜0．01)，DM患者血清PON活性低于正常对照者(F＝16．90，P＜0．01)；(2)PON活性与空腹血清胰岛素及C—P水平无明显相关(r＝0.113，P＞0．05，r＝0．109，P＞0．05)；(3)Logistic回归分析表明，PON活性(P＜0．01)是DR的独立变异危险因素。结论 PON活性变化与DR的发病有关。     

Ⅱ型糖尿病视网膜血流的动态研究

应用彩色多谱勒检测６０例Ⅱ型糖尿病患者的视网膜中央动、静脉血流状况。２／３无视网膜病变的糖尿病人已出现动脉收缩期峰值血流速度（ＰＳＶ）、加速度（Ａ）、舒张末期血流最大速度（ＥＤＶ）显著下降（分别是Ｐ＜０．０５、０．００１，０．００１）。背景型视网膜病变者，静脉回流速度显著增快（Ｐ＜０．０１）。结果表明：Ⅱ型糖尿病临床视网膜病变前期已有视网膜血流动力学的显著改变。     

Knowledge of ocular complications of diabetes in community-based people with type 2 diabetes: The Fremantle Diabetes Study II

AimsTo assess knowledge of diabetes-related eye disease in Australians with type 2 diabetes and its associations with diabetic retinopathy (DR), other ocular complications and vision-related quality of life.MethodsA random sample from the Fremantle Diabetes Study Phase II cohort (n = 360) was invited to participate. Knowledge was assessed using 10 multiple-choice questions covering how diabetes affects the eyes, frequency of ophthalmic screening, risk factors, prevention, available treatments, and prognosis. DR was assessed from fundus photographs. Multiple linear regression was used to identify independent associates of the knowledge score (KS).ResultsWe included 264 participants (mean ± SD age 72.1 ± 9.2 years, 56.8% male, median [IQR] diabetes duration 15.4 [11.1–22.3] years). The mean ± SD KS out of 10 was 5.3 ± 1.8. Most (67%) participants knew diabetes can affect the eye and lead to blindness. Only 13.6% knew that DR screening intervals depend on risk factors. Those with moderate non-proliferative DR (NPDR) or worse had a better knowledge score (B = 1.37,P = 0.008) after adjusting for age (B = ?0.03, P = 0.004) and education beyond primary school (B = 1.75, P < 0.001).ConclusionsOverall knowledge of diabetes-related ocular complications was suboptimal. Education targeting eye disease may benefit people with type 2 diabetes who are older, less well educated and/or who have no DR/mild NPDR.     

Limited joint mobility, Dupuytren's contracture and retinopathy in type 1 diabetes: association with cigarette smoking

To examine the associations between cigarette smoking, connective tissue changes, and diabetic retinopathy, a detailed smoking history was elicited from 150 normotensive non-diabetic subjects, and from 266 randomly selected adult patients with Type 1 diabetes, after examination for limited joint mobility, Dupuytren's contracture, and diabetic retinopathy. Mean insulin dose and current glycosylated haemoglobin concentrations were comparable in diabetic smokers and non-smokers. The historical duration of smoking correlated with the duration of diabetes (r = 0.72, p less than 0.001). In diabetic patients limited joint mobility was positively associated with retinopathy, being found in 73/147 (50%) patients with retinopathy compared with 20/114 (18%) without retinopathy (chi 2 = 28.9, p less than 0.001), and also with Dupuytren's contracture, 19/34 (56%) of patients with limited joint mobility having Dupuytren's contracture, compared with 76/232 (33%) of patients without Dupuytren's contracture (chi 2 = 7.05, p less than 0.01). Limited joint mobility was observed in 50% of diabetic smokers compared with 25% of non-smokers (odds ratio = 2.87 (corrected for diabetes duration), 95% confidence interval 1.64-5.01). Diabetic retinopathy was weakly associated with smoking (odds ratio 1.09; 95% confidence interval 0.60-1.96). There was however an increased prevalence of background retinopathy among male smokers (50% vs 29%; chi 2 = 6.88, p less than 0.01). In non-diabetic males limited joint mobility was observed in 37% of smokers but only in 11% of non-smokers (NS), while 33% of smokers and 8% of non-smokers had Dupuytren's contracture (p = 0.012). These results suggest that cigarette smoking contributes to the development of extra-articular connective tissue changes in both diabetic patients and non-diabetic subjects, and possibly to the development of diabetic retinopathy.     

Plasma homocysteine is associated with nonproliferative retinopathy in patients with type 2 diabetes without renal disease

Background and aimsThis study aimed to assess the role of plasma homocysteine (Hcy) in the development of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes (T2DM) without chronic kidney disease.MethodsThis was a cross-sectional study that included 94 T2DM. Hcy, serum 25-hydroxy (25-OH) vitamin D, vitamin B12, and folate were determined by the CMIA method. NPDR was determined according to the EURODIAB retinal photography methodology and optical coherence tomography (OCT) of the macula.ResultsCompared to patients without NPDR, patients with NPDR had longer diabetes duration (p < 0.001), higher Hcy (p < 0.001), lower vitamin B12 (p = 0.028) and lower estimated glomerular filtration rate (eGFR) (p = 0.004). NPDR was positively associated with diabetes duration (p < 0.001), HbA₁c (p = 0.049) and Hcy (p < 0.001), and negatively with vitamin B12 (p = 0.027) and eGFR (p = 0.005). Logistic regression analyses showed that diabetes duration (OR = 1.13, p < 0.001), Hcy (OR = 1.06, p = 0.047), and eGFR (OR = 0.96, p = 0.004) were the main predictors of NPDR in T2DM. Stepwise regression analyses showed that the best model for predicting Hcy (R2 = 0.104) included vitamins B12 and D.ConclusionsHigher Hcy is associated with NPDR and may play a role as a risk factor for its development in T2DM. Vitamins B12 and D seem to modify this association.     

Low cumulative incidence of proliferative retinopathy in childhood-onset type 1 diabetes: a 24-year follow-up study

Aims/hypothesis We estimated cumulative incidence of proliferative diabetic retinopathy (PDR) and risk factors for developing diabetic retinopathy (DR) in childhood-onset type 1 diabetes. Materials and methods A sample of 294 patients with childhood-onset type 1 diabetes (<15 years) diagnosed in Norway between 1973 and 1982 was examined for retinopathy at baseline between 1989 and 1990 and at follow-up from 2002 to 2003. At follow-up, mean age was 33 years (range: 21–44), mean diabetes duration 24 years (19–30) and total person-time contributed 7,152 person-years. Retinal photographs were taken at baseline and follow-up. Associations between baseline factors and PDR were estimated using Cox regression models. Results Overall, 262 of 294 (89.1%) developed DR from diabetes onset, of whom 31 developed PDR. The 25-year cumulative incidence of PDR was 10.9% (95% CI 7.3–14.5). Among 194 without retinopathy at baseline, 163 (84%) developed DR and nine (5%) progressed to PDR. Among 97 patients with non-proliferative DR at baseline, 19 (20%) progressed to PDR. Significant predictors for developing PDR were retinopathy at baseline (relative risk [RR]=3.71, 95% CI 1.59–8.68), HbA_1c (RR=2.05, 1.44–2.93), and triglycerides (RR=1.55, 1.06–1.95). Conclusions/interpretation Nine out of every ten patients diagnosed with type 1 diabetes developed DR, but only one out of ten developed PDR within their first 25 years of diabetes duration. The cumulative incidence of PDR is lower than previously reported from other countries. Potentially modifiable risk factors predict the development of DR and PDR.     

Renal outcomes in patients with type 2 diabetes with or without coexisting non-diabetic renal disease

Aims

We sought not only to determine the independent predictors of non-diabetic renal disease (NDRD) but also to investigate the impact of NDRD on renal outcomes in patients with type 2 diabetes who underwent renal biopsy and were followed-up longitudinally.

Methods

The present study was conducted by reviewing the medical records of 119 type 2 diabetic patients who underwent renal biopsy at Yonsei University Health System from January 1988 to December 2008.

Results

Renal biopsy findings declared that 43 patients (36.1%) had diabetic nephropathy alone, 12 (10.1%) had NDRD superimposed on diabetic nephropathy, and 64 (53.8%) had only NDRD. On multivariate analysis, the absence of diabetic retinopathy, higher hemoglobin levels, and shorter duration of diabetes were independent predictors of NDRD in these patients. During the follow-up period, end-stage renal disease (ESRD) developed in 33 patients (27.7%). On multivariate Cox regression, higher serum creatinine levels, higher systolic blood pressure, longer duration of diabetes, and the presence of diabetic nephropathy were identified as significant independent predictors of ESRD. When the presence of diabetic retinopathy was included in the multivariate model, higher serum creatinine levels, higher systolic blood pressure, and the presence of retinopathy were shown to be independent predictors of ESRD.

Conclusions

Since diabetic patients with NDRD have significantly better renal outcomes compared to patients with biopsy-proven diabetic nephropathy, it is important to suspect, identify, and manage NDRD as early as possible, especially in type 2 diabetic patients with short duration of diabetes and those without diabetic retinopathy or anemia.     

Non-diabetic renal disease in Croatian patients with type 2 diabetes mellitus

Aim

Our study aimed to examine the prevalence of non-diabetic renal disease in selected patients with type 2 diabetes mellitus and to determine important risk factors for non-diabetic renal disease.

Methods

We conducted retrospective analysis of clinical, laboratory and pathohistological data of type 2 diabetes mellitus patients in whom renal biopsies were performed from January 2004 to February 2013 at Dubrava University Hospital Zagreb Croatia (n = 80).

Results

According to renal biopsy findings, isolated diabetic nephropathy was found in 46.25%, non-diabetic renal disease superimposed on diabetic nephropathy in 17.5% and isolated non-diabetic renal disease in 36.25% of the patients. The most common non-diabetic renal diseases found were: membranous nephropathy, followed by IgA nephropathy and focal segmental glomerulosclerosis. In univariate analysis shorter duration of diabetes, independence of insulin therapy, lower levels of HbA1c and absence of diabetic retinopathy were found to be significant clinical predictors of non-diabetic renal disease. In multivariate analysis only independence of insulin therapy (OR 4.418, 95%CI = 1.477–13.216) and absence of diabetic retinopathy (OR 5.579, 95%CI = 1.788–17.404) were independent predictors of non-diabetic renal disease.

Conclusions

This study confirmed usefulness of renal biopsy in patients with type 2 diabetes mellitus, due to the high prevalence of non-diabetic renal disease found. Since non-diabetic renal disease are potentially curable, we should consider renal biopsy in selected type 2 diabetes mellitus patients with renal involvement, especially in those with absence of diabetic retinopathy and independence of insulin therapy.     

High-sensitivity C-reactive protein and impaired coronary vasoreactivity in young men with uncomplicated type 1 diabetes

Aims/hypothesis Elevated high-sensitivity C-reactive protein (hsCRP) concentrations indicate increased risk of future coronary events. The association between hsCRP and coronary vasoreactivity has not yet been examined in type 1 diabetic subjects.Methods We studied 18 young men who were non-smokers and who had uncomplicated type 1 diabetes. The diabetic subjects were divided into two groups, according to their median hsCRP concentration, as follows: (i) subjects with slightly elevated hsCRP (median 0.76 mg/l, range 0.47–4.73 mg/l, n=8); and (ii) subjects with low hsCRP (median 0.32 mg/l, range 0.11–0.35 mg/l, n=10). In addition we investigated 22 non-diabetic age-matched subjects (hsCRP: median 0.42 mg/l, range 0.11–1.31 mg/l). Resting myocardial blood flow and hyperaemic adenosine-stimulated flow during euglycaemic–hyperinsulinaemic clamp were determined using positron emission tomography and oxygen-¹⁵-labelled water.Results Diabetic subjects with slightly elevated hsCRP had significantly higher hsCRP concentrations than non-diabetic subjects (p=0.008). Resting myocardial blood flow was similar (NS) in diabetic subjects with slightly elevated hsCRP (0.79±0.19 ml·g^–1·min^–1) or low hsCRP (0.81±0.15 ml·g^–1·min^–1) and non-diabetic subjects (0.80±0.19 ml·g^–1·min^–1). Adenosine infusion induced a significant increase in blood flow in all study subjects (p<0.001) but was blunted in diabetic subjects with slightly elevated hsCRP (3.42±0.61 ml·g^–1·min^–1) when compared with diabetic subjects with low hsCRP (5.08±1.65 ml·g^–1·min^–1, p=0.02) or non-diabetic subjects (4.51±1.36 ml·g^–1·min^–1, p=0.04). Adenosine-stimulated flow was inversely correlated with hsCRP concentrations in all diabetic subjects (r=–0.70, p=0.001).Conclusions/interpretation In young subjects with uncomplicated type 1 diabetes, even slightly elevated hsCRP concentrations are associated with reduced coronary vasoreactivity.     

血清同型半胱氨酸水平与老年2型糖尿病视网膜病变的关系

目的　探讨血清总同型半胱氨酸 (Hcy)水平与老年人 2型糖尿病视网膜病 (DR)的关系及与其他危险因素的关系。方法　用免疫化学发光法检测 54例老年 2型糖尿病患者和 2 0例非糖尿病对照者的血清 Hcy水平 ,并收集其他相关危险因素资料。结果　 (1 )单因素分析结果显示 :DR组 (2 4例 )糖尿病病程、血浆糖化血红蛋白 (Hb A1 C)、血清甘油三酯 (TG)和 Hcy水平明显高于 2型糖尿病无视网膜病组 (NDR) (30例 )和非糖尿病对照组 (P<0 .0 5) ;(2 )血清 Hcy水平与 Hb A1 C呈正相关 ,与空腹胰岛素 (FINS)水平呈负相关 (P<0 .0 5) ;(3)多元 Logistic回归分析表明 ,血清Hcy水平增高是老年 DR的独立变异危险因素。结论　血清 Hcy水平增高与老年 DR的发病有关。