Diabetic macular edema and its relationship to renal microangiopathy: a sample of Type I diabetes mellitus patients in a 15-year follow-up study

PURPOSE: In the present study, our objective was to determine the epidemiological risk factors for the development of diabetic macular edema, especially attendant on renal diabetic lesion (microalbuminuria or overt nephropathy) in 112 Type I diabetic patients after 15 years. METHODS: This is a 15-year follow-up study of a cohort of 112 consecutive Type I (insulin-dependent) diabetes mellitus patients without diabetic retinopathy or nephropathy who were enrolled in 1990. We studied the incidence of diabetic macular edema and its risk factors. The epidemiological risk factors included in the study were as follows: gender, diabetes duration, glycated hemoglobin (HbA1c) levels, arterial hypertension, macroangiopathy, triglyceride levels, fractions of cholesterol [high-density lipoprotein cholesterol and low-density lipoprotein (LDL) cholesterol], and cigarette smoking. RESULTS: The incidence of diabetic macular edema after 15 years was as follows: the focal form of diabetic macular edema was present in 13 (11.6%) patients and the diffuse form of macular edema was present in 10 (8.9%) patients, among 23 (20.5%) patients. The following factors were significant in the development of diabetic macular edema: high levels of LDL-cholesterol (P=.013), high levels (>7.5%) of HbA1c (P=.021), the presence of macroangiopathy (P=.022), the severity of diabetic retinopathy (P=.029), the presence of arterial hypertension (P=.037), and the presence of overt nephropathy (P=.047). Microalbuminuria was not significant in logistic regression (P=.587), and cigarette smoking was not significant (P=.976). The relationship between diabetic macular edema and duration of diabetes presented two peaks of incidence: first in patients with 15-20 years' duration of diabetes mellitus, and second in patients with >35 years' duration. CONCLUSIONS: In summary, our data suggest that better control of glycemia, LDL-cholesterol levels, and blood pressure in Type I diabetes mellitus patients may be beneficial in reducing the incidence of diabetic macular edema. Finally, our data validate the current guidelines for ophthalmologic care for the detection of diabetic macular edema over the long-term course of diabetes.     

What may be gained from standard photocoagulation during early worsening of diabetic retinopathy? An observational study in type-1 diabetic patients after tightening of glycaemic control.

OBJECTIVE: To assess the outcome of laser photocoagulation treatment for rapidly progressing diabetic retinopathy, socalled early worsening, subsequent to a rapid improvement of glycemic control. For the purpose of this study, early worsening was defined as any incidence or progression of retinopathy that followed a reduction in HbA1c by > 2% within 6 months.MATERIAL AND METHODS: Retrospective observational study in type-1 diabetic patients in a university diabetes center.PATIENTS: 23 patients with early worsening were identfied during a 16-year period, with a mean age of 25 years, duration of diabetes of 12 years, and glycated hemoglobin HbA1c of 12.4%; retinopathy was absent or mild nonproliferative at baseline. Focal, and/or panretinal laser coagulation was performed according to standard ETDRS criteria. Retinal pathology and visual acuity was followed-up for 12-120 months.RESULTS: Improving metabolic control induced mild non-proliferative retinopathy without macular edema in 4 patients, which regressed without treatment. In 19 patients, symptomatic diabetic maculopathy developed with macular edema, resolving by focal coagulation in 3 patients. Of the remaining 16 patients, 14 developed proliferative retinopathy (7 of whom despite focal, grid or scatter coagulation pretreatment), and were treated by full panretinal coagulation. In 7 of the 14 patients with proliferative retinopathy, vitreous hemorrhages occurred requiring pars plana vitrectomy. Proteinuria, polyneuropathy, and impaired vision prior to laser treatment were indicative of poor prognosis. Visual acuity > 0.3 in at least one eye was preserved in 22 of the 23 patients.CONCLUSIONS: In patients with type-1 diabetes mellitus and early worsening of diabetic retinopathy, the benefit of standard laser photocoagulation was limited, and particularly in the presence of symptomatic macular edema.     

Update diabetische Retinopathie und Makulopathie

Diabetic retinopathy and macular edema are still the most common causes of blindness in the working-aged population. Thus it is important to be familiar with the evidence-based treatment methods available. Laser coagulation is the treatment of choice in the case of clinically significant focal, diabetic macular edema (focal application) and of proliferative diabetic retinopathy (panretinal application) Panretinal laser coagulation is also an option in the case of severe non-proliferative diabetic retinopathy, when risk factors such as poor compliance, suboptimal glycemic or blood pressure control, among other factors, are present. The value of vitreoretinal surgery is undisputed in the case of advanced diabetic retinopathy with non-resorbent severe vitreous or subhyaloid hemorrhage or vitreoretinal traction with relatively fresh or imminent macular detachment. Only adequate intraoperative panretinal laser coagulation can prevent post-operative complications as a result of retinal ischemia, such as recurrent hemorrhage, retinal detachment or rubeotic secondary glaucoma. Functional results of therapy, however, depend on the extent of ischemic damage to the retina caused by underlying microangiopathy, underlining the necessity for optimal prevention and adequate screening, as well as prompt initiation of therapy.     

Vascular Endothelial Growth Factor Inhibitors for Diabetic Retinopathy

The prevalence of diabetes is growing at epidemic rates in the USA. Diabetic retinopathy develops in a large proportion of patients and is a leading cause of blindness worldwide. Systemic management of diabetic retinopathy has included glycemic, hypertension, and lipid control. Local ophthalmic treatment in the form of focal/grid or panretinal laser photocoagulation has been shown to prevent vision loss in diabetic edema and proliferative diabetic retinopathy, respectively. The introduction of anti-vascular endothelial growth factor for diabetic macular edema and retinopathy has provided clinicians with improved clinical outcomes with potentially less damaging effects than laser.     

Association of manganese superoxide dismutase gene polymorphism (V16A) with diabetic macular edema in Korean type 2 diabetic patients

This study was designed to investigate whether V16A polymorphism of the manganese superoxide dismutase (Mn-SOD) gene is associated with the development of type 2 diabetes mellitus and with progression of diabetic retinopathy (DR) and diabetic macular edema (DME). We simultaneously analyzed insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene in the 16th intron to avoid its confounding effect. A total of 192 nondiabetic subjects and 304 type 2 diabetic patients were included in the study. Diabetic retinopathy was classified as nonretinopathy, nonproliferative retinopathy, and proliferative retinopathy. Diabetic macular edema was defined as thickening of the retina and/or hard exudates within a 1-disk diameter of the center of the macula. Diabetic macular edema was further classified into focal, diffuse, and ischemic types. The A allele frequency of the Mn-SOD gene was not different between nondiabetic and type 2 diabetic subjects, between the normotensive and hypertensive groups, between the DR (-) and DR (+) groups, and among the stages of DR. In the DR (+) group, the DME (+) group had a lower A allele frequency than that of the DME (-) group. In the DME (+) group, focal, diffuse, and ischemic types were found in 8, 23, and 6 patients, respectively. The A allele frequency of each type was 0.188, 0.109, and 0.0. The D allele frequency of the angiotensin-converting enzyme gene did not differ in any of the comparisons. Clinical and laboratory parameters of the A allele carriers were not different from those of the noncarriers except for the prevalence of hypertension and DME. Hypertension, diabetic duration, and insulin therapy were related to DR. The A allele, hypertension, and insulin therapy were associated with DME. In conclusion, our results suggest that V16A polymorphism of the Mn-SOD gene is not related to the development of diabetes and progression of DR, but is associated with DME in Korean type 2 diabetic patients.     

Scanning laser edema index: A reliable tool to correlate with diabetic retinopathy and systemic risk factors?

To correlate Heidelberg Retina Tomograph (HRT) derived macular edema (DME) index with severity of diabetic retinopathy and systemic factors. A total of 300 diabetic patients were recruited for the study for each of them a value for the macular edema index was obtained using the HRT II. Patients' age, gender, duration and type of diabetes mellitus, latest HbA1c result and presence or absence of co-morbid factors (hypertension, ischemic heart disease, nephropathy) were recorded together with the stage of diabetic retinopathy. These were correlated with DME. Out of 300 patients, HRT defined macula edema was seen in 68 patients (22.6%). There is a wider and higher range (95% percentile) of macula edema index in the severe non proliferative diabetic retinopathy (NPDR) group. Independent samples t test showed significant difference between the severe NPDR group and no DR group (p<0.001), mild NPDR group (p<0.05) and moderate NPDR group (p<0.05). A higher macula edema index was also found to have a low degree of correlation with more advanced stages of retinopathy (r=0.310; p<0.001). Also nephropathy showed a strong and significant correlation with DME. Hypertension had moderately significant correlation with DME. This study found no correlation between ischemic heart disease and DME. HRT derived scanning laser edema index is a reliable objective tool to evaluate diabetic retinopathy and systemic risk factors.     

Renal and retinal microangiopathy after 15 years of follow-up study in a sample of Type 1 diabetes mellitus patients

PURPOSE: In the present study, the objective is to determine the epidemiological risk factors in the appearance of diabetic retinopathy and nephropathy in 112 Type 1 diabetic patients after 15 years. METHODS: A 15-year follow-up study was done in a cohort of 112 consecutive Type 1 (IDDM) diabetes mellitus patients without diabetic retinopathy or nephropathy at enrolment in 1990. We studied the incidence of diabetic retinopathy and/or microalbuminuria. The epidemiological risk factors included in the study were gender, diabetes duration, HbA(1c) levels, arterial hypertension, levels of triglycerides and fractions of cholesterol (HDL-cholesterol and LDL-cholesterol). RESULTS: The incidence of diabetic retinopathy was 55.40% at the end of study; the risk factors associated were duration of diabetes mellitus (P<.001), high levels of HbA(1c) (P=.009), presence of arterial hypertension (P=.007) and high levels of LDL-cholesterol (P=.002). The incidence of microalbuminuria was 41.07% and that of overt nephropathy, 19.60%; the risk factors associated were high levels of HbA(1c) (P<.001) and presence of arterial hypertension (P=.023). At the end of study, four groups of patients were formed: patients without microalbuminuria or retinopathy, patients with microalbuminuria only, patients with retinopathy only and patients with retinopathy and microalbuminuria. From the results of the discriminate analysis, we may assume that for the development of retinal lesions only, in the diabetes mellitus, the duration of the disease, the high levels of HbA(1c) and the arterial hypertension are most important, and for the development of renal and retinal lesion simultaneously, the important factor is poor control of glycemia measured by levels of HbA(1c) and arterial hypertension. CONCLUSIONS: In conclusion, microalbuminuria correlated well with severe forms of diabetic retinopathy, and at the end of the study, two groups of patients had been configured: the first group had developed only diabetic retinopathy, and the second, their patients with diabetic retinopathy together with renal lesion (microalbuminuria). For the first group, the duration of diabetes mellitus was the most important risk factor, and for the second group, the levels of HbA(1c) and blood pressure were the most important.     

Serum lipid profile in diabetic macular edema

PurposeTo evaluate the correlation of lipid profile and clinical presentation of macular edema in Type 2 diabetes mellitus (DM) patients.Materials and MethodsThe study included 20 patients with chronic diabetic macular edema and plaque-like hard exudates (Group 1), 20 patients with diabetic macular edema (Group 2), and 20 DM patients but without retinopathy (Group 3). Diabetic retinopathy was classified according to the Early Treatment Diabetic Retinopathy Study grading system. Sample t test was used to evaluate the association between the fasting serum lipid [total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL)], glycosylated hemoglobin (HbA1c), fasting blood glucose, creatinine levels, and the clinical findings. P values <.05 were considered statistically significant.ResultsThere was no difference between fasting serum lipids and HbA1c levels. Duration of diabetes was shorter in Group 3 than in Groups 1 and 2. Patients in Group 1 had longer duration of diabetes than others (P<.05). Creatinine levels in Group 1 were higher than in other groups (P<.05). Although there was no correlation between fasting blood glucose and HbA1c levels, HbA1c was higher in all three groups from the baseline-normal limits (P<.05).ConclusionNo correlation was found between serum lipid levels and macular edema severity, but the duration of diabetes was demonstrated as a significant factor in the progression of macular edema. High HbA1c levels in all patients highlight the importance of intense glycemic control in diabetic patients.     

How does hypertension affect your eyes?

Hypertension has profound effects on various parts of the eye. Classically, elevated blood pressure results in a series of retinal microvascular changes called hypertensive retinopathy, comprising of generalized and focal retinal arteriolar narrowing, arteriovenous nicking, retinal hemorrhages, microaneurysms and, in severe cases, optic disc and macular edema. Studies have shown that mild hypertensive retinopathy signs are common and seen in nearly 10% of the general adult non-diabetic population. Hypertensive retinopathy signs are associated with other indicators of end-organ damage (for example, left ventricular hypertrophy, renal impairment) and may be a risk marker of future clinical events, such as stroke, congestive heart failure and cardiovascular mortality. Furthermore, hypertension is one of the major risk factors for development and progression of diabetic retinopathy, and control of blood pressure has been shown in large clinical trials to prevent visual loss from diabetic retinopathy. In addition, several retinal diseases such as retinal vascular occlusion (artery and vein occlusion), retinal arteriolar emboli, macroaneurysm, ischemic optic neuropathy and age-related macular degeneration may also be related to hypertension; however, there is as yet no evidence that treatment of hypertension prevents vision loss from these conditions. In management of patients with hypertension, physicians should be aware of the full spectrum of the relationship of blood pressure and the eye.     

Association between subclinical hypothyroidism and severe diabetic retinopathy in Korean patients with type 2 diabetes

The association between subclinical hypothyroidism (SCH) and microvascular complications of type 2 diabetes is unclear. We examined whether SCH is associated with diabetic retinopathy or nephropathy in Korean patients with type 2 diabetes. Data from 489 patients who visited the diabetes clinic at a university hospital between 2001 and 2007 were analyzed retrospectively. Participants were evaluated for glycemic control, thyroid function, and diabetic retinopathy and nephropathy. Diabetic retinopathy was classified into five grades. Diabetic nephropathy was assessed by the presence of albuminuria. Patients in the SCH group had a higher proportion of women, older age, longer duration of diabetes, higher systolic and diastolic blood pressure, and higher insulin resistance index compared with the euthyroid group. No significant difference in family history of diabetes or body mass index was found between groups. The prevalence of severe diabetic retinopathy (severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy) was significantly higher in the SCH group than the euthyroid group (32.8% vs. 19.6%, P = 0.036), whereas no between-group difference was found in the prevalence of diabetic nephropathy. After adjustment for potential confounding factors (HbA1c, BMI, duration of diabetes, diabetic nephropathy, and hypertension) by multivariate logistic regression analysis, SCH remained significantly associated with severe diabetic retinopathy (odds ratio 2.086 (95% CI, 1.010-4.307), P = 0.047). These results suggest that SCH was independently associated with severe diabetic retinopathy in patients with type 2 diabetes. Further prospective studies are required to confirm the association between SCH and diabetic retinopathy.     

Surgical treatment of diabetic retinopathy

Laser treatment is effective for diabetic macular oedema and proliferative diabetic retinopathy. In focal diabetic macular oedema, laser coagulation of the microaneurisms prevents the leakage of liquid through their walls. In diffuse macular oedema, laser photocoagulation not only destroys the microaneurisms but probably also hereby causes stimulation of proliferation activity of endothelial cells in retinal capillaries and veins. For some patients with diabetic retinopathy there is a progression of retinal findings and complications arise that require surgery within the eye - pars plana vitrectomy (PPV). In general PPV is indicated in diabetic retinopathy in the following cases: vitreous opacity, traction disorders.     

Cardiovascular risk factors in pre-pubertal Malays: effects of diabetic parentage

Diabetes prevalence is increasing rapidly in Asian populations but the influence of a family history of diabetes on cardiovascular risk is unknown. To assess this relationship, 120 urban-dwelling Malays were recruited to a cross-sectional case-control study. Sixty were pre-pubertal children, 30 of diabetic parentage (Group 1) and 30 with no diabetes family history (Group 2). Group 1 and 2 subjects were the offspring of adults with (Group 3) or without (Group 4) type 2 diabetes. Subjects were assessed for clinical and biochemical variables defining cardiovascular risk. Principal component analysis assessed clustering of variables in the children. Group 1 subjects had a higher mean waist:hip ratio, diastolic blood pressure and HbA(1c) than those in Group 2, and a lower HDL:total cholesterol ratio (P<0.03). Although there were no correlations between Group 1 and 3 subjects for cardiovascular risk variables, significant associations were found in Groups 2 and 4, especially HbA(1c) and insulin sensitivity (P< or =0.004). Of five separate clusters of variables (factors) identified amongst the children, the strongest comprised diabetic parentage, HbA(1c), insulin sensitivity and blood pressure. Features of the metabolic syndrome are becoming evident in the young non-obese children of diabetic Malays, suggesting that lifestyle factors merit particular attention in this group.     

住院老年2型糖尿病患者微血管病变的相关因素分析

目的探讨老年2型糖尿病患者微血管病变的构成比及相关因素。方法用回顾性分析的方法研究2003年～2010年于卫生部北京医院住院治疗的年龄≥60岁的2型糖尿病患者876例,分为糖尿病肾病(DN)组和非糖尿病肾病(非DN)组,糖尿病视网膜病变(DR)组和非糖尿病视网膜病变(非DR)组,糖尿病周围神经病变(DPN)组和非糖尿病周围神经病变(非DPN)组,计算DN、DR、DPN构成比,比较患者的临床特点,并探寻老年2型糖尿病患者DR、DN、DPN的相关因素。结果 (1)DN构成比为34.5%,DR构成比为42.4%,DPN构成比为82.3%。(2)DN与非DN两组间体质量指数(BMI)、糖尿病病程、高血压病程、收缩压(SBP)、舒张压(DBP)、空腹血糖(FBS)、糖化血红蛋白(HbA1c)、空腹胰岛素(Fins)、高密度脂蛋白胆固醇(HDL)、甘油三酯(TG)、尿酸(UA)均有显著性差异(P<0.05或P<0.01);DR与非DR两组间仅糖尿病病程、SBP、空腹C肽(FCP)有显著性差异(均P<0.01);DPN与非DPN两组间年龄、糖尿病病程、HbA1c、TC、LDL有显著性差异(P<0.05或P<0.01)。(3)Logistic回归结果显示,DN与SBP、HbA1c、FBS、HDL、UA、糖尿病病程有关(OR值分别为1.022、1.098、1.075、0.501、1.004,1.048,P<0.05或P<0.01);DR与SBP、HbA1c、糖尿病病程有关(OR值分别为1.017、1.102、1.097,P<0.05或P<0.01);DPN与HbA1c、LDL、糖尿病病程、年龄有关(OR值分别为1.226、1.370、1.041、1.058,P<0.05或P<0.01)。结论对于老年2型糖尿病患者,DN、DR、DPN均与糖尿病病程和HbA1c有关,控制血糖对防治微血管病变意义重大,综合控制血糖、血压、血脂、尿酸可以更好的防治糖尿病微血管并发症。     

Ten-year incidence of diabetic retinopathy and macular edema. Risk factors in a sample of people with type 1 diabetes

Aims

To determine the 10-year incidence of diabetic retinopathy (DR) and macular edema (DME), and its relationship with its risk factors in a sample of type 1 diabetes mellitus.

Methods

A total of 334 patients without diabetic retinopathy at baseline underwent a 10-year prospective study, the risk factors included: age, gender, diabetes duration, HbA1c, LDL-C, HDl-C, TC/HDL-C ratio, ApoA1, ApoB, ApoB/ApoA1 ratio, and triglycerides were recorded. Risk factors for diabetic macular edema (DME) were also recorded.

Results

The 10-year incidence of any DR was 35.90%, and 11.07% developed DME. The risk factors for DR and DME were: diabetes duration, high glycosylated level, and arterial hypertension, and overt nephropathy was well correlated with DME. The lipid study demonstrated that ApoB/ApoA1 ratio was significant for any DR [HRR: 0.594 (0.416-0.848), p = 0.01], and DME [HRR: 0.601 (0.433-0.894), p = 0.009]. The TC/HDL ratio was only significant for DME [HRR: 0.624 (0.440-0.886), p = 0.008]; other lipids values were not significant for any groups studied.

Conclusions

In the present study, the ApoB/ApoA1 ratio was significant to the 10-year incidence of diabetic retinopathy and to macular edema; and the TC/HDL ratio was significant to a 10-year incidence of macular edema.     

Sight-threatening retinopathy is associated with lower mortality in type 2 diabetic subjects: a 10-year observation study

AIMS: To study associations between diabetic retinopathy and development of stroke, myocardial infarction and death in type 2 diabetic patients. METHODS: During a 10-year observation period, 363 type 2 diabetic patients (diagnosis > or =30 years of age) attending an outpatient clinic were studied regarding the prevalence and incidence of retinopathy and associated risk factors, i.e., (HbA(1c), blood pressure, albuminuria, plasma creatinine, age, sex and diabetes duration) in relation to the development of myocardial infarction, stroke and death. The degree of retinopathy was classified as no retinopathy, background or sight-threatening retinopathy, i.e., clinically significant macular edema, severe non-proliferative or proliferative retinopathy. RESULTS: During the study period, 62 patients had had myocardial infarction, 54 stroke and 99 patients died. Patients with sight-threatening retinopathy at baseline (n=41) had a 2.2-fold increased (p<0.01) risk for death compared to patients with no or background retinopathy, even when controlled for medical risk factors. When adjusted for medical risk factors, patients with no retinopathy at baseline (n=226) who remained without retinopathy or developed background retinopathy (n=187) during the study period, had a 3.6-fold increased risk for death (95% CI, 1.1, 11.8), (p=0.03), compared to patients who developed sight-threatening retinopathy (n=39), while the incidence of myocardial infarction did not differ. More patients who developed sight-threatening retinopathy were treated with ACE inhibitors than patients who did not (41% versus 24%; p=0.03). CONCLUSION: Despite more medical risk factors, patients who developed sight-threatening retinopathy had lower mortality compared to patients with no or background retinopathy at follow-up. More patients who developed sight-threatening retinopathy were treated with ACE inhibitors but this seemed not to have influenced the lower mortality rate in this group, whereas the use of ACE inhibitors in patients who did not develop sight-threatening retinopathy was connected with lower mortality rate.     

Progression of diabetic retinopathy during improved metabolic control may be treated with reduced insulin dosage and/or somatostatin analogue administration -- a case report.

It is well known that intensified insulin treatment of poorly controlled type 1 diabetic patients may worsen an existing diabetic retinopathy (DR). This observation has been explained by an insulin-induced stimulation of the GH/IGF-I axis. Here, we report on three cases, where the progression of DR during intensified metabolic control was treated with manipulation of insulin therapy and/or by administration of octreotide. Serum concentrations of IGF-I, IGFBP-3, insulin, cystatin C, creatinine, endogenous creatinine clearance and HbA1c-levels were assessed by routine laboratory methods; serum IGF-I bioactivity was estimated by a highly specific kinase receptor activation assay. Visual acuity and retinopathy stage was assessed by established clinical methods including fluorescein angiography. After glycaemic control was improved by intensified insulin therapy, serum IGF-I levels acutely increased. Subsequently, DR progressed to an advanced stage ("florid retinopathy"), with macular edema, and proliferation of new vessels (in two cases). Immediate reduction of insulin dosage and administration of octreotide lowered serum total IGF-I levels (and IGF-I bioactivity as measured in one patient). Subsequently, macular edema resolved partly, and visual acuity improved, allowing laser photocoagulation to be performed. In conclusion, in poorly controlled type 1 diabetic patients, intensified insulin therapy is able to cause florid DR with acute macular edema. These sight-threatening changes may improve by short-term reduction of insulin dosage or by administration of octreotide, and we speculate that this may be related to down-regulation of (serum) IGF-I.     

Systolic blood pressure response to exercise in type 1 diabetes families compared with healthy control individuals

OBJECTIVE: Oxidative stress is increased in type 1 diabetes families. Since oxidative damage is a mediator of vascular injury and familial predisposition to hypertension increases the risk of hypertension and diabetic nephropathy, we studied blood pressure responses to exercise and cardiovascular risk factors in type 1 diabetes families. METHODS: Thirty-five type 1 patients, 74 first-degree relatives, and 95 healthy individuals without established coronary heart disease underwent a cycle ergometer test. Examination included medical history, lifestyle questionnaire, body weight, blood pressure, and laboratory tests [fasting plasma glucose and insulin, haemoglobin A1c (HbA1c), plasma lipids, C-reactive protein, fibrinogen, folate, plasma thiols, and albumin excretion rate]. RESULTS: Diabetic patients had higher plasma glucose, HbA1c, folate, and albuminuria, while lower plasma thiols than controls; relatives differed from controls in higher plasma total cholesterol and albuminuria, lower plasma thiols. No patient presented exercised-induced angina. Diabetic patients achieved a higher maximal exercise systolic blood pressure (similar workload); systolic pressure remained high during recovery. Relatives showed higher values of systolic pressure at peak exercise (same workload). The following were associated with an abnormal blood pressure response to exercise: diastolic blood pressure and HbA1c in the control sample; disease duration and fibrinogen in the diabetic group; plasma low-density lipoprotein (LDL) cholesterol, body mass index (BMI), housework, and plasma thiols among relatives. CONCLUSION: An abnormal blood pressure response to exercise testing has been identified for the first time in asymptomatic normotensive non-diabetic relatives of type 1 diabetics, which was associated with indices of metabolic syndrome and oxidative damage. Moreover, in healthy normotensive non-diabetic control individuals (without a family history of type 1 diabetes), the systolic blood pressure response to exercise was significantly correlated with HbA1c levels.     

Diabetic retinopathy, visual acuity, and medical risk indicators. A continuous 10-year follow-up study in Type 1 diabetic patients under routine care

The objective of this study was to describe incidence and progression of diabetic retinopathy in relation to medical risk indicators as well as visual acuity outcome after a continuous follow-up period of 10 years in a Type 1 diabetic population treated under routine care. The incidence and progression of retinopathy and their association to HbA_1c, blood pressure, urinary albumin, serum creatinine levels, and insulin dosage were studied prospectively in 452 Type 1 diabetic patients. The degree of retinopathy was classified as no retinopathy, background, or sight-threatening retinopathy, i.e. clinically significant macular edema, severe nonproliferative, or proliferative retinopathy. Impaired visual acuity was defined as a visual acuity <0.5 and blindness as a visual acuity ≤0.1 in the best eye. In patients still alive at follow-up (n=344), 61% (69/114) developed any retinopathy, 45% (51/114) background retinopathy, and 16% (18/114) sight-threatening retinopathy. Progression from background to sight-threatening retinopathy occurred in 56% (73/131). In 2% (6/335), visual acuity dropped to <0.5 and in less than 1% (3/340) to ≤0.1. Patients who developed any retinopathy and patients who progressed to sight-threatening retinopathy had higher mean HbA_1c levels over time compared to those who remained stable (P<.001 in both cases). Patients who developed any retinopathy had higher levels of mean diastolic blood pressure (P=.036), whereas no differences were seen in systolic blood pressure levels between the groups. Cox regression analysis, including all patients, showed mean HbA_1c to be an independent risk indicator for both development and progression of retinopathy, whereas mean diastolic blood pressure was only a risk indicator for the incidence of retinopathy. Metabolic control is an important risk indicator for both development and progression of retinopathy, whereas diastolic blood pressure is important for the development of retinopathy in Type 1 diabetes. The number of patients who became blind during 10 years of follow-up was low.     

Metabolic control and prevalence of microvascular complications in young Danish patients with Type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood.

AIMS: After Danish nationwide investigations (1987, 1989) demonstrated unacceptable blood glucose control in unselected young diabetic patients, we set out to estimate the present glycaemic control and the prevalence of microvascular complications in a cohort of children and adolescents participating in the two previous studies. METHODS: This follow-up represents 339 patients (47% of the inception cohort), median age 21.1 years (range 12.0-26.9), median diabetes duration 13.2 years (range 8.9-24.5). A standardized questionnaire, fundus photographs (with central reading) and a physical examination were performed. HbA1c and overnight albumin excretion rate (AER) were analysed centrally. RESULTS: Although 88% (n= 309) of the young persons were treated with three or more daily insulin injections, HbA1c (nondiabetic range 4.3-5.8, mean 5.3%) was 9.7+/-1.7% (mean+/-SD). Males had higher HbA1c values than females (P < 0.015). Mean daily insulin dose was 0.92+/-0.25 IU.kg(-1).24h(-1). Microalbuminuria (AER > 20-150 microg/min) and macroalbuminuria (AER > 150 microg/min) were found in 9.0% and 3.7% of the patients, respectively, and was associated with increased diastolic blood pressure (P<0.01) and presence of retinopathy (P<0.01). Retinopathy was present in approximately 60% of the patients and was associated with age, diabetes duration, HbA1c, diastolic blood pressure and AER (all P<0.01). Subclinical neuropathy (vibration perception threshold by biothesiometry > 6.5 V) was found in 62% and showed a significant association with age, linear height, diastolic blood pressure (all P < 0.01) and diabetic retinopathy (P = 0.01). CONCLUSIONS: In spite of the majority of the patients being on multiple insulin injections, only 11% had HbA1c values below 8% and the prevalence of diabetic microvascular complications in kidneys, eyes and nerves was unacceptable high.     

Is blood pressure a predictor of the incidence or progression of diabetic retinopathy?

The relationship between blood pressure and the 4-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Younger- (n = 891) and older-onset (n = 987) persons participating in baseline and follow-up examinations were included. Blood pressure was measured using the Hypertension Detection and Follow-up Program protocol. Retinopathy was determined from stereoscopic fundus photographs. In the younger-onset group, comparing the highest with the lowest quartile of systolic blood pressure, the relative risk for developing any diabetic retinopathy was 1.8 and for diastolic blood pressure it was 1.2; for progression of diabetic retinopathy, it was 1.1 and 1.3 for systolic and diastolic blood pressure, respectively. After controlling for other risk variables, systolic blood pressure remained a significant predictor of the incidence of diabetic retinopathy; diastolic blood pressure was of borderline significance in predicting progression in the younger-onset group. Blood pressure was not related to incidence or progression of retinopathy either in the older-onset group using insulin or the older-onset group not using insulin.