The Wisconsin epidemiologic study of diabetic retinopathy: VIII. The incidence of retinal photocoagulation

The incidence of focal and panretinal photocoagulation and its relationship to demographic and other characteristics were examined in a population-based study of people with diabetes in southern Wisconsin. For participants whose age at diagnosis was less than 30 years, who were taking insulin, and who had not been previously treated with photocoagulation, the 4 year incidence of panretinal photocoagulation (10.8%) was significantly higher (p<.0001) than the rate of focal and/or grid photocoagulation of the macula (4.3%). For those whose age at diagnosis was 30 years or older and who had not been previously treated with photocoagulation, the incidence rates of panretinal photocoagulation (4.4%) and focal and/or grid photocoagulation of the macula (3.1%) were not significantly different (p=.11). At follow-up examination, 33.8% of the eyes of younger onset persons and 57.7% of the eyes of older onset persons with Diabetic Retinopathy Study high risk characteristics for severe visual loss had never received panretinal photocoagulation. These relatively high frequencies of untreated eyes in need of panretinal photocoagulation remain a concern.     

Cardiovascular disease in type 1 diabetes mellitus

The association between type 1 diabetes and coronary heart disease has become very clear since the late 1970. It has been demonstrated that there is an important increased risk in morbidity and mortality caused by coronary artery disease in young adults with type 1 diabetes compared with the non diabetic population. The underlying pathogeneses is still poorly understood. While the role of glycemic control in the development of microvascular disease complication is well established its role in CVD in patients with DM1 remains unclear with epidemiologic studies reporting conflicting data. Recent findings from the DCCT/EDIC showed that prior intensive diabetes treatment during the DCCT was associated with less atherosclerosis, largely because of reduced level of HbA1c during the DCCT. The improvement of glycemic control itself appeared to be particularly effective in younger patients with shorter duration of the disease. Other analyses suggested the glycemia may have a stronger effect on CAD in patients without than in those with albuminúria. Other major determinants of coronary artery disease are the components of metabolic syndrome and the surrogate measure of insulin resistence: eGDR. It is proposed that patients with DM1 should have aggressive medical therapy, risk factor modification and careful monitoring not only of his blood sugar but also of the other processes involved in the atherosclerotic process, mostly the ones with family history of type 2 diabetes.     

The Wisconsin epidemiological study of diabetic retinopathy: a review

The WESDR has provided precise estimates of the prevalence, and 4-year incidence and progression of diabetic retinopathy. It has provided evidence of a possible causal relationship between specific risk factors, such as hyperglycemia and the development and progression of retinopathy. Our data support current recommendations for ophthalmologic examinations for people with diabetes. In 1990 we will reexamine the cohort to determine the 10-year incidence and progression of diabetic retinopathy, macular edema, and visual impairment.     

干预多重危险因素对2型糖尿病微血管病、心血管病、病死率的效果：Steno-2研究

多年来，干预心血管危险因素对预防糖尿病慢性并发症的重要性已成共识，但干预性研究多限于某一种因素，如血糖、血压或血脂，同时对多重因素进行干预并已取得成果的试验目前仅有Steno-2研究^[1-4]，故其经验受到重视。     

Periodontal disease,smoking, cardiovascular complications and mortality in type 1 diabetes

AimTo assess the role of periodontal disease (PD) as a predictor of coronary artery disease (CAD) and mortality in a prospective type 1 diabetes (T1D) cohort and to evaluate the role of smoking in this relationship.MethodsData were based on 320 participants of the Pittsburgh Epidemiology of Diabetes Complications study of T1D who, during 1992–94, received a partial mouth periodontal exam, and who were followed for up to 19 years to ascertain complication incidence. PD was defined as clinical attachment loss of ≥4 mm for at least 10% of the examined sites. Predictors of all-cause mortality; Hard CAD (CAD death, myocardial infarction or revascularization), and Total CAD (Hard CAD, angina, ischemic ECG) were assessed using Cox models.ResultsDuring 19 years of follow-up, 33.7% (97/288) developed CAD, 27.3% (83/304) developed Hard CAD, and 16.9% (54/320) died. Among current smokers, 46.4% (26/56) developed CAD, 42.7% (24/56) developed Hard CAD and 29.5% (18/61) died. PD was not associated with all-cause mortality, although it was a significant predictor of both CAD (HR = 1.12, CI = 1.01–1.23) and Hard CAD (HR = 1.30, CI = 1.11–1.51). As smoking modified the PD-CAD and PD-Hard CAD associations, analyses were stratified by smoking status. PD was associated with an increased risk of CAD (HR = 1.25, CI = 1.03–1.50) and Hard CAD (HR = 1.85, CI = 1.17–2.93) only among smokers.ConclusionPD was a significant predictor of CAD and Hard CAD among current smokers with T1D.     

An epidemiologic approach to the study of retinopathy: the Pittsburgh diabetic morbidity and retinopathy studies

Diabetic retinopathy was studied in two cohorts of insulin-dependent diabetics (IDDs) from the Children's Hospital of Pittsburgh. The first cohort (n = 696) consisted of IDDs of long duration. Severe retinopathy was self-reported in 70% of this cohort by 30 years duration of diabetes. Associations between severe retinopathy, hypertension and smoking were observed. In order to examine the relationship between metabolic control and early diabetic retinopathy, a second cohort of adolescent IDDs (n = 58) were referred for standardized fluorescein angiography. Sixty-four percent had early retinopathy. None had proliferative changes. Significant differences in individual mean whole blood glycosylated hemoglobin (GHb), averaged over 3 years before angiography, were consistently seen between those with and without early retinopathy. Also, the number of microaneurysms was positively correlated with individual mean GHb. Before the advent of GHb testing, those IDDs who later had retinopathy were more likely to have experienced at least one hospitalization for diabetic ketoacidosis. These observations provide strong support that poor metabolic control preceded the development of diabetic retinopathy. Results are consistent with the hypothesis that improvement of metabolic control early in the course of IDDM may prevent or delay the development of the early changes of diabetic retinopathy.     

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.     

Proliferative retinopathy and proteinuria predict mortality rate in type 1 diabetic patients from Fyn County, Denmark

Aims/hypothesis We evaluated the effect of diabetic retinopathy on 25 year survival rate among a population-based cohort of type 1 diabetic patients from Fyn County, Denmark. Methods In 1973 all diabetic patients from Fyn County, Denmark with onset before the age of 30 years as of 1 July 1973 were identified (n = 727). In 1981, only 627 patients were still alive and resident in Denmark. Of these, 573 (91%) participated in a clinical baseline examination, in which diabetic retinopathy was graded and other markers of diabetes measured. Mortality rate was examined in a 25 year follow-up and related to the baseline examination. Results Of the 573 patients examined at baseline in 1981 and 1982, 297 (51.8%) were still alive in November 2006. Of the others, 256 (44.7%) had died, three (0.5%) had left Denmark and 17 (3%) were of unknown status. Age- and sex-adjusted HRs of mortality rate were 1.01 (95% CI 0.72–1.42) and 2.04 (1.43–2.91) for patients with non-proliferative and proliferative retinopathy respectively at baseline compared with patients with no retinopathy. After adjusting for proteinuria, HR among patients with proliferative retinopathy lost statistical significance, but still remained 1.48 (95% CI 0.98–2.23). The 10 year survival rate of patients who had proliferative retinopathy as well as proteinuria at baseline was 22.2% and significantly lower (p < 0.001) than in patients with proteinuria only (70.3%), proliferative retinopathy only (79.0%) or neither (86.6%). Conclusions/interpretation Proliferative retinopathy and proteinuria predict mortality rate in a population-based cohort of type 1 diabetic patients. In combination they act even more strongly. Non-proliferative diabetic retinopathy did not affect survival rate.     

Cardiovascular disease in diabetes type 2: current concepts

Type 2 diabetes is a major and accelerating public health challenge. Between 1980 and 2014, a period of just 35 years, the number of adults with diabetes globally is estimated to have increased from 108 to 422 million, due not only to sharply rising obesity rates, but also to increasing population size, longer life expectancy, and rising prevalence of diabetes worldwide. Overall, worldwide age‐standardized adult diabetes prevalence doubled from 4.3% to 9.0% in men and from 5.0% to 7.9% in women. The largest increases in diabetes type 2 have been demonstrated in low‐ and middle‐income countries, whilst rises in high‐income countries have been less marked, or even flat. Diabetes type 2 rates in low‐ and middle‐income countries now in many instances surpass those in high‐income countries, in response to changes in lifestyle. One factor of particular concern are the large relative increases in type 2 diabetes amongst young individuals observed in many countries, their higher overall risk factor burden, long exposure to hyperglycaemia and greater risk of complications over the life course. Type 2 diabetes is increasingly found to be a heterogeneous condition, where risk of cardiovascular disease that traditionally has been estimated at 2–4 times that of the nondiabetic population varies substantially with diabetes phenotype and accordingly diabetes does not confer the same increase in relative or absolute risk in all people. New research shows that excess risk varies substantially with type of outcome, age, glycaemic control, the presence of renal complications and other factors. Heart failure, previously less recognized that other cardiovascular conditions, is increasingly coming into focus, because of strong links with poor glycaemic control and obesity. The knowledge about risk of cardiovascular disease in diabetes is almost entirely derived from high‐income countries, whereas there is comparatively very little data from low‐ and middle income countries, where the majority of persons with type 2 diabetes live, and where management in many cases is far from optimal. The reductions in cardiovascular disease incidence and mortality now observed in high‐income countries are encouraging, because this reinforces the fact that improvement is possible and that a near‐normal, or even normal life‐expectancy can be achieved in subtypes of type 2 diabetes.     

Antioxidants and an inhibitor of advanced glycation ameliorate death of retinal microvascular cells in diabetic retinopathy

BACKGROUND: Pericyte ghosts and acellular capillaries are well known as early histological changes resulting from diabetic retinopathy. These histological changes mean that the cell death of retinal microvessels has accelerated. It was reported that apoptosis of retinal microvascular cells (RMCs) was increased in diabetic patients. Therefore, we investigated apoptosis of RMCs in Goto-Kakizaki (GK) rats, a type 2 diabetic model, and involvement with antioxidants (a combination of vitamins C and E) or a novel inhibitor of advanced glycation, OPB-9195. METHODS: GK rats were treated with the antioxidants combination or OPB-9195 for 36 weeks. We obtained isolated preparations of the vascular network from their retinas by trypsin digestion. Apoptosis of retinal vascular cells was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: We found that apoptosis of RMCs was increased in the diabetic GK rats. Furthermore, a combination of vitamins C and E and an advanced glycation end-products inhibitor mostly inhibited this increased apoptosis. CONCLUSIONS: We concluded that apoptosis of RMCs was a good marker that indicates the progression of diabetic retinopathy in GK rats. Both oxidative stress and the accumulation of advanced glycation end-products appears to promote the apoptosis of retinal microvascular cells, and antioxidants or advanced glycation end-products inhibitors might ameliorate diabetic retinopathy.     

Diabetic retinopathy in predicting diabetic nephropathy in patients with type 2 diabetes and renal disease: a meta-analysis

Aims/hypothesis

The aim of this meta-analysis is to determine the predictive value of diabetic retinopathy in differentiating diabetic nephropathy from non-diabetic renal diseases in patients with type 2 diabetes and renal disease.

Methods

Medline and Embase databases were searched from inception to February 2012. Renal biopsy studies of participants with type 2 diabetes were included if they contained data with measurements of diabetic retinopathy. Pooled sensitivity, specificity, positive predictive value, negative predictive value and other diagnostic indices were evaluated using a random-effects model.

Results

The meta-analysis investigated 26 papers with 2012 patients. The pooled sensitivity and specificity of diabetic retinopathy to predict diabetic nephropathy were 0.65 (95% CI 0.62, 0.68) and 0.75 (95% CI 0.73, 0.78), respectively. The pooled positive and negative predictive value of diabetic retinopathy to predict diabetic nephropathy were 0.72 (95% CI 0.68, 0.75) and 0.69 (95% CI 0.67, 0.72), respectively. The area under the summary receiver operating characteristic curve was 0.75, and the diagnostic odds ratio was 5.67 (95% CI 3.45, 9.34). For proliferative diabetic retinopathy, the pooled sensitivity was 0.25 (95% CI 0.16, 0.35), while the specificity was 0.98 (95% CI 0.92, 1.00). There was heterogeneity among studies (p?<?0.001), and no publishing bias was identified.

Conclusions/interpretation

Diabetic retinopathy is useful in diagnosing or screening for diabetic nephropathy in patients with type 2 diabetes and renal disease. Proliferative diabetic retinopathy may be a highly specific indicator for diabetic nephropathy.     

Cardiovascular disease risk prediction in type 1 diabetes: accounting for the differences

Present analyses used data from the Pittsburgh Epidemiology of Diabetes Complications Study, a prospective study of subjects with childhood type 1 diabetes (T1D), diagnosed between 1950 and 1980. Baseline exams took place 1986-1988 with biennial exams since. The Framingham risk equation was applied to generate the probability of risk for coronary heart disease (CHD) (MI, CHD death, or Q-waves) in 552 CHD free subjects who experienced 42 events over the 10-year follow-up period. Probabilities were split in to deciles. Expected and observed events were compared and demonstrated poor prediction. Risk factors previously found to be associated with CHD in T1D other than those in the Framingham risk function (age, smoking, cholesterol/HDLc, systolic blood pressure) were compared within the highest risk deciles. In men, elevated fibrinogen (p=0.007), white blood cell count (WBC) (p=0.037), albumin excretion rate (AER) (p=0.0001), and lower HDLc (p=0.048) were predictive. In females, higher Beck Depression Inventory (p=0.008), HbA1 (p=0.008), AER (p=0.01), LDLc (p=0.007), fibrinogen (p=0.006), WBC (p=0.005), non-HDLc (p=0.0005), WHR (p=0.003), and estimated glucose disposal rate (p=0.002) were associated. Risk factors not considered by the Framingham risk equation may account for the lack of fit and should be examined further.     

OCT is not useful for detection of minimal diabetic retinopathy in type 1 diabetes

Optical coherence tomography (OCT) has been proven useful in measuring retinal thickness (RT) in patients with diabetes, although with discordant results in different studies. We examined RT in patients with type 1 diabetes (T1D) with or without minimal diabetic retinopathy (MDR) to test whether OCT is able to identify early retinal changes and potential correlations with metabolic parameters. RT of 102 patients with T1D (53 females, 49 males, aged 27.03 ± 7.4 years) and of 42 healthy controls was examined, with analysis of nine different sectors (fovea, four pericentral and four peripheral sectors). According to the results of basal fundus photography, patients were divided into two groups, without MDR (48 cases) and with MDR (54 cases). Patients with proliferative DR or macular edema were excluded. No difference was found between patients with or without MDR and the control group for all OCT parameters investigated. Mean HbA1c of the last 5 years (P < 0.001), microalbuminuria (P = 0.002), total (P = 0.046) and LDL cholesterol (P = 0.007) and triglyceride (P < 0.001) levels were higher in patients with MDR, along with higher prevalence of hypertension (P = 0.013), younger age at diagnosis (P = 0.018) and longer diabetes duration (P < 0.001) with regard to the patients without MDR and controls, although no significant correlation between these parameters and RT was found. Our study suggests that MDR without macular edema in patients with T1D cannot be detected with OCT. Therefore, the conventional diagnostic methods are mandatory to detect early DR.     

Early-onset type 2 diabetes: high risk for premature diabetic retinopathy

Aim

To examine the relationship between early-onset type 2 diabetes (T2D) and retinopathy in relation to the burden, severity, the extent of its premature development and associated predictive risk factors.

Methods

A cross sectional study using the hospital diabetes register and eye screening database to identify T2D subjects and to ascertain retinopathy severity. Early and later-onset cohort were defined as age of diagnosis <40 and >40 years respectively.

Results

2516 subjects were identified of which 455 were diagnosed below 40 years. After 10 years of diagnosis, the prevalence of overall retinopathy was significantly higher in the early-onset cohort (p < 0.05). For significant retinopathy (SigDR), there was a non-significant trend of higher prevalence with increasing diabetes duration in the early-onset cohort. The rate of increase for SigDR was greater in the early-onset cohort who experienced similar burden of SigDR up to 20 years earlier than the later-onset cohort. Hypertension (p < 0.05), suboptimal glycaemic control (p < 0.05) and long diabetes duration (p < 0.05) were associated with risk of retinopathy whilst lower age of diagnosis and dyslipidaemia were not significant predictive factors.

Conclusions

Early-onset T2D subjects are at risk of developing premature retinopathy driven predominantly by hypertension and prolonged exposure to suboptimal diabetes control.     

An association between the sarcolemmal membrane-associated protein gene and microvascular endothelial diabetic retinopathy in patients with type 2 diabetes mellitus: A preliminary case control study

Background and aimsDiabetic retinopathy (DR) is one of the most common microvascular diabetic complications. Sarcolemmal membrane-associated protein (SLMAP) has been implicated in playing a role in microvascular endothelial dysfunction. This study aimed to assess the significance of SLMAP rs17058639C > T gene polymorphism among patients with type 2 diabetes mellitus (T2DM) and its relevance to microvascular endothelial diabetic retinopathy.MethodsWe conducted this case-control study on 100 individuals divided into 60 participants with T2DM and 40 healthy controls. Patients with T2D were stratified into two groups: 40 patients with DR and 20 patients with diabetic non-retinopathy (DNR). Patients with T2DM were compared with age- and sex-matched healthy controls. Fundus examinations were conducted to detect microvascular endothelial changes. The polymorphism of SLMAP rs17058639C > T gene was identified by real-time polymerase chain reaction (RT-PCR) TaqMan allelic discrimination.ResultsPatients with DR have significantly increased glycated hemoglobin (HbA1c) compared to patients with DNR (P < 0.001). There was no statistically significant difference found between diabetic and control groups regarding the frequency of SLMAP rs17058639C > T genotypes. The homozygous CC genotype was the most common variant among patients with DR; however, the results did not reach statistical significance.ConclusionsDiabetic retinopathy is correlated with poor glycemic control, and SLMAP rs17058639C > T polymorphism was associated with microvascular endothelial DR in patients with T2DM, although further studies with a large sample size are needed to confirm our findings.     

Cardiovascular disease in type 1 diabetes: A review of epidemiological data and underlying mechanisms

Cardiovascular disease (CVD) is highly prevalent in patients with type 1 diabetes (T1D) and a major cause of mortality. CVD arises earlier in life in T1D patients and is responsible for a significant reduction of at least 11 years’ life expectancy. Also, the incidence of CVD is much more pronounced in patients with T1D onset at an earlier age. However, the factors responsible for increased atherosclerosis and CVD in T1D are not yet totally clarified. In addition to the usual cardiovascular (CV) risk factors, chronic hyperglycaemia plays an important role by promoting oxidative stress, vascular inflammation, monocyte adhesion, arterial wall thickening and endothelial dysfunction. Diabetic nephropathy and cardiac autonomic neuropathy are also associated with increased CVD in T1D. In fact, the CVD risk remains significantly increased even in well-controlled T1D patients who have no additional CV risk factors, indicating that other potential factors are likely to be involved. Hypoglycemia and glucose variability could enhance CV disease by promoting oxidative stress, vascular inflammation and endothelial dysfunction. Furthermore, even well-controlled T1D patients show significant qualitative and functional abnormalities of lipoproteins that are likely to be implicated in the development of atherosclerosis and premature CVD. In addition, recent data suggest that a dysfunctional immune system, which is typical of autoimmune T1D, might also promote CVD possibly through inflammatory pathways. Moreover, overweight and obese T1D patients can manifest additional CV risk through pathophysiological mechanisms resembling those observed in type 2 diabetes (T2D).