Automated perimetric changes following panretinal photocoagulation in diabetic retinopathy

Sixty eyes--30 with severe nonproliferative diabetic retinopathy (NPDR) and 30 with proliferative diabetic retinopathy (PDR)--underwent argon laser panretinal photocoagulation (PRP). Static perimetry (Humphrey automated visual field analyzer 630, Threshold Prog Central 30-1 and Peri 30/60-1) was done 1 day before and 6 weeks after the initial laser treatment. One day before treatment, the fields of the NPDR and PDR eyes differed mainly in the central field affection: the PDR eyes had more localized areas of markedly decreased retinal sensitivity and, therefore, a higher initial mean deviation value and higher corrected pattern standard deviation values. However, peripheral retinal sensitivity was equally depressed in the NPDR and PDR eyes. Six weeks after treatment, central retinal sensitivity had significantly improved in all of the eyes, although more so in the eyes with severe NPDR. This study suggests that static-perimetry-guided PRP is an effective treatment for diabetic retinopathy, especially severe NPDR.     

Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18

PURPOSE: To identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: Multivariable Cox models were constructed to evaluate the strength and statistical significance of baseline risk factors for development of high-risk PDR and of SVLV. RESULTS: The baseline characteristics identified as risk factors for high-risk PDR were increased severity of retinopathy, decreased visual acuity (or increased extent of macular edema), higher glycosylated hemoglobin, history of diabetic neuropathy, lower hematocrit, elevated triglycerides, lower serum albumin, and persons with mild to moderate nonproliferative retinopathy, younger age (or type 1 diabetes). The predominant risk factor for development of SVLV was the prior development of high-risk PDR. The only other clearly significant factor was decreased visual acuity at baseline. In the eyes that developed SVLV before high-risk proliferative retinopathy was observed, baseline risk factors were decreased visual acuity (or increased extent of macular edema), older age (or type 2 diabetes), and female gender. CONCLUSIONS: These analyses supported the view that the retinopathy-inhibiting effect of better glycemic control extends across all ages, both diabetes types, and all stages of retinopathy up to and including the severe nonproliferative and early proliferative stages and the possibility that reducing elevated blood lipids and treating anemia slow the progression of retinopathy.     

Activated eosinophils in esophagitis in children: a transmission electron microscopic study

OBJECTIVE: To describe the interval between first appearance of mild nonproliferative diabetic retinopathy (NPDR) and first appearance of neovascularization (NV) in type I diabetes. SETTING: A longitudinal study of 269 patients followed up annually. PARTICIPANTS: Participants had insulin-dependent diabetes and were free of proliferative diabetic retinopathy in both eyes at the baseline visit. MAIN OUTCOME MEASURE: Stereoscopic color fundus photographs of each eye at each study visit, graded for features of retinopathy. RESULTS: Among the 305 eyes for which the duration of diabetes at the first appearance of mild NPDR could be determined, NV developed in 28 by the end of the study. Survival analysis showed that the later the onset of mild NPDR was, the shorter the time from onset of mild NPDR to onset of NV (relative hazard for each additional year to onset of mild NPDR, 1.22; 95% confidence interval, 1.10-1.35). Adjustment for systolic and diastolic blood pressure, proteinuria, and glycosylated hemoglobin (Hgb A10) levels did not change the relative hazard estimate for onset of mild NPDR. Higher levels of Hgb A10 were associated with a shorter time from onset of mild NPDR to onset of NV (relative hazard, 1.26; 95% confidence interval, 1.05-1.51 [after adjusting for time at onset of mild NPDR]), as were higher levels of diastolic blood pressure, although not significantly (relative hazard for 10-mm Hg increase in diastolic blood pressure, 1.52; 95% confidence interval, 0.82-2.83 [adjusting for onset of mild NPDR, Hgb A10 level, systolic blood pressure, and proteinuria]). Neither proteinuria nor systolic blood pressure had an effect on time from onset of mild NPDR to onset of NV, after adjustment for time at onset of mild NPDR, Hgb A10 level, and diastolic blood pressure. CONCLUSION: Later onset of mild NPDR is not necessarily associated with delayed development of NV in patients with type I diabetes. Caution must therefore be used in assessing the value of interventions that delay the onset of mild NPDR without evidence of delayed onset of NV.     

Early electrocardiographic abnormalities in Trypanosoma cruzi-seropositive children

OBJECTIVE: The incidence of diabetic nephropathy in type 2 diabetes differs widely by race. Although clinical proteinuria is reportedly more common in East Asian type 2 diabetic patients than in their Caucasian counterparts, data on the incidence of microalbuminuria are not available. This study was undertaken to investigate the incidence and the determinants of microalbuminuria in Korean type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A cohort of 188 Korean type 2 diabetic patients with initial normoalbuminuria were followed prospectively for 5.5 +/- 0.9 years in an outpatient clinic of a university hospital. The incidence of elevated urinary albumin excretion (UAE) (> 20 micrograms/min) and its relationship with baseline characteristics and follow-up data were determined. RESULTS: Of the 146 patients who finished the study, 37 showed persistently elevated UAE during follow-up, giving an incidence of 52/1,000 person-years. Age, duration of diabetes, and baseline UAE were significantly higher in the progressors than in the nonprogressors. More patients in the progressor group had retinopathy at baseline and at the end of follow-up. The mean values of fasting plasma glucose, HbA1, and systolic and diastolic blood pressure during the follow-up period were significantly higher in the progressors than in the nonprogressors. Cox proportional hazards analysis revealed that presence of retinopathy, duration of diabetes, mean fasting plasma glucose, and mean systolic blood pressure during follow-up are independent variables that have a statistically significant influence on the development of microalbuminuria. CONCLUSIONS: The incidence of microalbuminuria in Korean type 2 diabetic patients is lower than that reported in Pima Indians with type 2 diabetes but is as high as that in Caucasians with type 1 diabetes. Presence of diabetic retinopathy, poor glycemic control, and high blood pressure are risk factors for development of microalbuminuria in Koreans with type 2 diabetes.     

Lipoprotein(a) in android obesity and NIDDM

OBJECTIVE: To assess the level of serum lipoprotein(a) [Lp(a)] in nonobese and obese NIDDM subjects with android body distribution. RESEARCH DESIGN AND METHODS: Serum Lp(a) levels were measured in 30 long-standing NIDDM patients (duration of diabetes 12.5 +/- 3 years, mean +/- SD), with 15 of the patients being obese of android distribution (BMI > 30 kg/m2 and waist-to-hip ratio > 0.8). In addition, there were 15 android obese nondiabetic subjects and 10 healthy subjects serving as the control group. RESULTS: All groups of patients in this study (diabetic, obese, and obese diabetic) showed significantly higher levels of Lp(a) than the healthy control group. Lp(a) concentrations were significantly higher in NIDDM patients with android type of obesity than in nondiabetic androids (24.1 +/- 5.6 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Significantly greater levels of Lp(a) were found in nonobese subjects with diabetes when compared with obese subjects without diabetes (22.3 +/- 4.1 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Furthermore, Lp(a) serum concentrations were not dependent on the degree of glycemic control (controlled NIDDM 23.6 +/- 5.0 vs. uncontrolled NIDDM 21.4 +/- 2.7 mg/dl, NS), but were much greater in subjects with diabetes complicated by vascular disease (complicated 26.3 +/- 5.0 vs. uncomplicated 20.5 +/- 2.7 mg/dl, P < 0.001). No correlation was found between Lp(a) and other lipid parameters in this study. CONCLUSIONS: Lp(a) levels are significantly elevated in both android-obese and nonobese NIDDM patients regardless of the degree of glycemic control. Lp(a) is an independent risk factor showing greater elevations in those subjects complicated with diabetic vascular diseases.     

Full panretinal photocoagulation and early vitrectomy improve prognosis of florid diabetic retinopathy

BACKGROUND: Florid diabetic retinopathy (FDR) is a rare form of proliferative diabetic retinopathy (PDR) that is characterized by a bilateral rapidly progressive, very severe ischemic retinopathy. Florid diabetic retinopathy was reported to carry a high risk of blindness. This study was conducted to determine whether visual prognosis of FDR can be improved by appropriate photocoagulation and surgical management. METHODS: The authors retrospectively studied 20 patients (40 eyes) who were treated from October 1978 to February 1994. Systemic risk factors, visual acuity, complete ocular examination, and fundus findings, as well as fluorescein angiography, were analyzed with respect to photocoagulation and surgical management. Mean follow-up was 3.6 years. RESULTS: All patients had poorly controlled type I diabetes (mean duration, 13.5 years), which often was associated with systemic complications. Mean initial visual acuity was equal to or better than 20/40 in 32 eyes (80%). During the course of the study, high-risk PDR was observed in 38 eyes (95%) and vitreous hemorrhage occurred in 26 eyes (65%). Extensive full subconfluent panretinal photocoagulation was performed completely in 37 eyes (92.5%). Vitrectomy was necessary in 15 eyes (37.5%). Macular edema was present in 30 eyes (75%). Major complications included retinal detachment that required surgery (2 eyes, 5%) and neovascular glaucoma (2 eyes, 5%). However, final visual acuity was equal to or better than 20/40 in 23 eyes (57.5%) and less than 5/200 in only 4 eyes (10%). CONCLUSION: These results suggest that aggressive treatment of FDR with extensive panretinal photocoagulation and early vitrectomy, when necessary, may result in a much better prognosis than has been reported previously.     

Resting ECG changes in long term survivors after carotid endarterectomy

PURPOSE: The aqueous flare intensity and pupillary size were studied before and after instillation of 10% phenylephrine and 4% pilocarpine in eyes with diabetes mellitus (DM). METHODS: Twenty-three patients with DM type I were compared with 30 age-matched controls, and 25 patients with DM type II were compared with 30 age-matched controls. Patients with DM were divided into two groups: 1) with mild-moderate nonproliferative diabetic retinopathy (NPDR), and 2) with advanced diabetic retinopathy (DR) which includes moderate-severe, severe NPDR and proliferative DR. The aqueous flare intensity and the horizontal diameter of the pupil were measured before and 60 minutes after topical instillation of 10% phenylephrine and 60 min after topical administration of 4% pilocarpine. RESULTS: Degree of induced mydriasis after phenylephrine instillation was not significantly different between diabetic groups and controls. Significantly less pronounced miosis was observed after stimulation of cholinergic receptors by pilocarpine in eyes with mild-moderate NPDR with DM type II and in eyes with advanced DR with DM type I and type II when compared to controls (p<0.05). Phenylephrine decreased flare intensity in all groups without a significant difference between groups. Pilocarpine instillation increased flare intensity in all groups as compared to flare intensity before any treatment. Also, a significantly smaller increase in flare intensity in eyes with advanced retinopathy in both DM type I and type II was found when compared to controls (p<0.05). CONCLUSION: Pharmacological response to cholinergic stimulation on pupil size and flare intensity is weaker in advanced stages of DR.     

Relationship between prorenin, IGF-I, IGF-binding proteins and retinopathy in diabetic patients

Plasma prorenin and renin, serum insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP-2 and IGFBP-3) concentrations were measured in 22 randomly selected male and female patients with insulin-dependent diabetes mellitus (IDDM) or non-IDDM (NIDDM). Plasma prorenin concentration was significantly elevated in patients with proliferative retinopathy (1869.5 +/- 785.0 mUL-1, mean +/- SEM) compared to patients with nonproliferative retinopathy (325.5 +/- 73.2 mUL-1, P < 0.003) and those without retinopathy (318.6 +/- 47.3 mUL-1, P < 0.007). Similarly, serum insulin-like growth factor-I (IGF-I) concentration in patients with proliferative retinopathy (126.3 +/- 21.5 micrograms L-1) was significantly higher than in patients with nonproliferative retinopathy (126.3 +/- 14.85 micrograms L-1, P < 0.004) and without retinopathy (135.2 +/- 37.26, P < 0.05). There was moderately strong positive correlation between plasma prorenin and serum IGF-I concentrations (r = 0.56, P < 0.01). Plasma prorenin concentration was uninfluenced by change in renal function (creatinine clearance, serum creatinine or BUN), but IGF-I levels were inversely related to creatinine clearance (r = 0.67, P < 0.002). There was no demonstrable relationship between IGF-binding proteins and prorenin or renin concentrations. In view of some overlap between plasma prorenin and serum IGF-I concentrations in diabetic patients with proliferative and nonproliferative retinopathy, measurement of both markers may be more useful in predicting the development of proliferative retinopathy in patients with diabetes mellitus than either measurement alone.     

In vitro chemosensitivity of chronic lymphocytic leukaemia to purine analogues--correlation with clinical course

OBJECTIVE: To compare the risk for diabetic retinopathy in non-Hispanic white, non-Hispanic black, and Mexican-American adults with type 2 diabetes in the U.S. population. RESEARCH DESIGN AND METHODS: Representative population-based samples of people aged > or = 40 years in each of the three racial/ethnic groups were studied in the 1988-1994. Third National Health and Nutrition Examination Survey (NHANES III). Diagnosed diabetes was ascertained by medical history interview, and undiagnosed diabetes by measurement of fasting plasma glucose. A fundus photograph of a single eye was taken with a nonmydriatic camera, and a standardized protocol was used to grade diabetic retinopathy. Information on risk factors for retinopathy was obtained by interview and standard laboratory procedures. RESULTS: Prevalence of any lesions of diabetic retinopathy in people with diagnosed diabetes was 46% higher in non-Hispanic blacks and 84% higher in Mexican Americans, compared with non-Hispanic whites. Blacks and Mexican Americans also had higher rates of moderate and severe retinopathy and higher levels of many putative risk factors for retinopathy. Blacks had lower retinopathy prevalence among those with undiagnosed diabetes. In logistic regression, retinopathy in people with diagnosed diabetes was associated only with measures of diabetes severity (duration of diabetes, HbA1c, level, treatment with insulin and oral agents) and systolic blood pressure. After adjustment for these factors, the risk of retinopathy in Mexican Americans was twice that of non-Hispanic whites, but non-Hispanic blacks were not at higher risk for retinopathy. These risks were similar when people with undiagnosed diabetes were included in the logistic regression models. CONCLUSIONS: The prevalence and severity of diabetic retinopathy is greater in non-Hispanic blacks and Mexican Americans with type 2 diabetes in the U.S. population than in non-Hispanic whites. For blacks, this can be attributed to their higher levels of risk factors for retinopathy, but the excess risk in Mexican Americans is unexplained.     

The rationale of argon green laser photocoagulation for diabetic maculopathy

To determine the effect of glycemic control on vitamin B12 (B12) metabolism in diabetes mellitus, we studied B12 metabolism in 19 diabetic patients with poor glycemic control and 15 normal individuals. The diabetic patients had significantly higher total B12 binding capacity (3303 +/- 963 pg/ml), higher serum B12 levels (1173 +/- 503 pg/ml) and unsaturated B12 binding capacity (2131 +/- 902 pg/ml) when compared with the normal controls, but there was no difference in R-binder levels and the B12 binding ratio between the two groups. During a 2-week admission to establish glycemic control, the fructosamine levels in the diabetic patients decreased from 556 to 428 mumol/l and the total B12 binding capacity as well as unsaturated B12 binding capacity were significantly improved to the normal range (P < 0.01), but serum B12 levels, R-binder levels and the B12 binding ratio were not changed. There was a significant association between serum fructosamine levels and the total B12 binding capacity in poorly controlled diabetic patients and the decrease of fructosamine was correlated significantly with the change of total B12 binding capacity and serum B12 levels in diabetic patients. These results indicate the effects of glycemic control on B12 metabolism in diabetes mellitus.     

Prevalence and risk factors for diabetic retinopathy in the multiethnic population of Mauritius

This study examines the prevalence of, and risk factors for, diabetic retinopathy in Asian Indian, Chinese, and Creole Mauritians in whom there is an increasing prevalence of non-insulin-dependent diabetes mellitus (NIDDM). As part of a population-based survey on the Indian Ocean island of Mauritius in 1992, glucose tolerance was classified using a 75-g oral glucose tolerance test on 6,553 persons. Subjects with newly diagnosed (n = 358) or known diabetes (n = 388), and a random sample of one in four subjects with impaired glucose tolerance (n = 165), had stereoscopic 45 degrees retinal photographs taken of three fields in the right eye after mydriasis. Photographs were graded according to a modified version of the Airlie House criteria. The prevalence of nonproliferative and proliferative retinopathy was: 14.5% and 0.3%, respectively, in newly diagnosed diabetic subjects; 42.0% and 2.3%, respectively, in known diabetic subjects; and 9.1% and 0%, respectively, in persons with impaired glucose tolerance. Muslim Indians had the lowest prevalence of retinopathy (10.8% and 34.0% for new and known diabetes, respectively), but after adjusting for other factors, this was significantly different only to Creoles (18.8% and 53.8%, respectively). Univariate analysis revealed significant differences between diabetic subjects with and without retinopathy in mean age, body mass index, fasting and 2-hour plasma glucose levels, systolic and diastolic blood pressure, fasting triglycerides, serum creatinine, and urinary albumin levels. For known diabetes, mean duration of diabetes and the proportion using insulin were also greater in those with retinopathy. Multivariate analysis using logistic regression confirmed that increasing duration of diabetes, fasting plasma glucose, systolic blood pressure, and urinary albumin concentration, and decreasing body mass index, were independently associated with retinopathy. The high prevalence of diabetic retinopathy observed in all major ethnic groups in Mauritius portends a serious public health problem, given the relative recency of the NIDDM epidemic in that country and the limited resources for laser photocoagulation. Strategies to minimize this problem among those already known to have diabetes should include strict control of plasma glucose and blood pressure.     

Pre-eclampsia is a potent risk factor for deterioration of retinopathy during pregnancy in Type 1 diabetic patients

The aim of the present study was to examine the influence of pregnancy on deterioration of retinopathy in patients with Type 1 diabetes mellitus. Sixty-five pregnant Type 1 diabetic women attending the University Hospital in Lund were studied retrospectively. The degree of retinopathy, and levels of HbA1c and blood pressure 12 months before, during, and 6 months after pregnancy were compared of those of 56 non-pregnant Type 1 diabetic women matched for age and duration of diabetes. For all patients, sight-threatening deterioration of retinopathy did not differ between the pregnancy group (9/65) and the control group (6/56). Over time, pregnant patients had lower HbA1c levels than controls (p < 0.001). Pregnant patients with sight-threatening deterioration of retinopathy had higher HbA1c levels than those without (p = 0.028 and the decrement in HbA1c between the 6-14th and the 20th week of gestation was more pronounced (p = 0.006). In those patients who developed pre-eclampsia during pregnancy, deterioration of retinopathy ocurred more frequently compared to those without pre-eclampsia (4/8 vs 5/65; p = 0.005). In conclusion, sight-threatening deterioration of retinopathy was not more common during pregnancy in IDDM patients than among age- and duration-matched control patients. In pregnant patients, deterioration of retinopathy was associated with the pregestational degree of metabolic control as well as with a rapidly improved glycaemic control acheived during pregnancy. Among those in whom deterioration occurred during pregnancy, pre-eclampsia was a potent risk factor.     

Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and diabetic retinopathy in subjects with IDDM and NIDDM

Angiotensin 1 converting enzyme (ACE) catalyses the step which generates angiotensin II, and also inactivates bradykinin, peptides which play a key role in modulating vascular tone. Plasma ACE levels are under genetic control and up to 50% of the variation is due to an insertion/deletion (I/D) polymorphism of ACE gene with highest levels found in DD homozygotes. Studies have shown an association of diabetic nephropathy and ischaemic heart disease with angiotensin converting enzyme gene polymorphism in subjects with diabetes. We examined the association between diabetic retinopathy and ACE gene insertion/deletion polymorphism in 363 subjects with NIDDM (aged 68.3 +/- 10.7 years; 201 male, 162 female), 186 subjects with IDDM (aged 42.4 +/- 15.0 years; 100 male, 86 female) and 98 controls. These subjects were characterized for ACE I/D polymorphism employing standard primers. Diabetic retinopathy was diagnosed by ophthalmoscopy through dilated pupils by an ophthalmologist and classified as non-proliferative or proliferative retinopathy. As expected, diabetic retinopathy was strongly associated with duration of diabetes (p < 0.001) in both IDDM and NIDDM. Any retinopathy was present in 51% subjects with IDDM and 49% of subjects with NIDDM, while 22% of IDDM subjects and 5% of subjects with NIDDM had proliferative retinopathy. The frequency of I allele was 0.477 vs 0.482 vs 0.510 and D allele was 0.523 vs 0.518 vs 0.490, among subjects with IDDM, NIDDM and controls, respectively. The frequency of ACE I/D genotype was similar in subjects with IDDM, NIDDM, and controls (chi 2 = 0.46, df = 4, p = ns). Presence or absence of retinopathy was not significantly associated with ACE genotype in subjects with IDDM (chi 2 = 3.42, df = 2, p = ns) or NIDDM (chi 2 = 0.51, df = 2, p = ns). Among subjects with retinopathy, there was no significant association between ACE genotype and type of retinopathy. Controlled for duration of diabetes, the frequency of I/D genotype was not significantly different in 271 subjects with retinopathy (IDDM and NIDDM combined) when compared with 86 subjects without retinopathy at 15 years or more after diagnosis of diabetes (chi 2 = 1.29, df = 2, p = ns). These findings indicate that I/D polymorphism of ACE gene is not a useful marker and is unlikely to play a major role in determining genetic susceptibility to diabetic retinopathy or the severity of diabetic retinopathy.     

beta-N-acetylglucosaminidase and beta-glucuronidase activities in insulin-dependent diabetic subjects with retinopathy

The serum activities of two lysosomal enzymes, beta-N-acetylglucosaminidase (EC 3.2.1.30, NAG) and beta-glucuronidase (EC 3.2.1.31, GLU), were determined in 41 insulin-dependent diabetics, 27 age-matched non-diabetic first-degree relatives of the diabetics and 103 age-matched non-diabetic blood-donors. The diabetics were divided into three groups on the basis of ophthalmoscopy: (1) no retinal abnormalities; (2) non-proliferative retinopathy; and (3) proliferative retinopathy. The activities of both serum enzymes were higher in diabetics (NAG 21.39 +/- 5.99; GLU 2.19 +/- 1.01) than in their relatives (NAG 17.22 +/- 3.99; GLU 1.62 +/-0.61). The diabetics with non-proliferative retinopathy had higher serum enzyme levels (NAG 24.05 +/- 6.26; GLU 2.60 +/- 1.06) than diabetics without retinopathy (NAG 17.88 +/- 3.00; GLU 1.69 +/ 0.64), whereas no statistically significant difference was found in patients with the proliferative form of retinopathy (NAG 18.67 +/- 6.28; GLU 1.99 +/- 1.04). In diabetics a positive correlation was found between serum beta-N-acetylglucosaminidase activity and blood glucose (p < 0.01), but not between beta-glucuronidase and blood glucose. Furthermore, the activities of both enzymes in diabetics correlated with the plasma triglyceride level (p < 0.05 for both correlations). No correlation was found between the enzyme levels and signs of other diabetic late complications.     

Plasma levels of pentosidine in diabetic patients: an advanced glycation end product

Nonenzymatic reactions between glucose and proteins yield advanced glycation end products (AGE) such as pentosidine. AGE accumulate in diabetic patients, alter the structure and function of tissue proteins, stimulate cellular response, and have thus been implicated in diabetic tissue damage. The present study was undertaken to assess the factors determining plasma total pentosidine level in diabetic patients and the possible relation between plasma pentosidine level and diabetic complications. In diabetic patients, including patients with renal failure, plasma pentosidine levels, assessed by HPLC assay, were correlated with serum creatinine (P < 0.0001). In patients with normal renal function, pentosidine levels were correlated with blood glucose control (hemoglobin Alc: P = 0.0028; fructoselysine: P = 0.0133), serum creatinine (P = 0.029), patient age (P = 0.0416), duration of diabetes (P = 0.0431), and total cholesterol (P = 0.0056) and LDL-cholesterol (P = 0.0208). Multiple regression analysis revealed an independent influence of hemoglobin Alc and serum creatinine on pentosidine levels (r2 = 0.216, P = 0.0026). Pentosidine levels were higher in patients with than in those without hypertension (P = 0.043) or ischemic heart diseases (P = 0.0061). No such differences were observed between patients with and without albuminuria or retinopathy. Multiple regression analysis revealed an independent influence of plasma pentosidine on the presence of hypertension (r2 = 0.129, P = 0.0382) and of plasma pentosidine and HDL-cholesterol on the presence of ischemic heart disease (r2 = 0.326, P = 0.0012). The present study demonstrated that plasma pentosidine level was significantly influenced by the quality of glycemic control and renal function. Pentosidine level was also correlated with hypertension and ischemic heart disease, and might be taken as a biomarker of diabetic cardiovascular risk.     

Exogenous interleukin-3 enhances IL-4 production by splenic CD4+ cells during the early stages of a Trichinella spiralis infection

We determined serum advanced glycation end-products (AGE) levels in patients with NIDDM and evaluated the relationship between these levels and diabetic complications. The subjects consisted of 125 patients (mean age, 59.2 +/- 11.1 years, duration of diabetes 11.6 +/- 8.9 years, mean HbA1c, 6.8 +/- 1.0%) with stable blood sugar control. Sixty-three healthy volunteers (mean age, 58.3 +/- 12.7 years) served as controls. Serum AGE were measured by a newly developed ELISA method. Serum AGE levels were significantly higher in the diabetic group compared with the normal control group (7.2 +/- 14.6 vs. 3.3 +/- 1.0 mU/ml, P < 0.05). Significant correlations were seen between serum AGE and the degree of diabetic nephropathy. Serum AGE levels of diabetic patients with proliferative retinopathy were significantly higher than those of patients without proliferative retinopathy (5.7 +/- 1.8 vs. 3.1 +/- 1.0 mU/ml, P < 0.025) in the patient groups whose serum creatinine levels were between 2.0 and 3.9 mg/dl, although serum creatinine levels of both groups were not significantly different. Serum AGE levels reflected the severity of diabetic complications, including nephropathy and retinopathy.     

Apolipoprotein(a) genetic polymorphism and serum lipoprotein(a) concentration in patients with peripheral vascular disease

Serum lipoprotein(a) (Lp(a)) levels were measured in 89 men with peripheral vascular disease (PVD) and 129 (100 male and 29 woman) healthy controls. Apolipoprotein(a) genetic polymorphism was determined by immunoblotting in all subjects. Patients with PVD had significantly higher serum Lp(a) levels than controls. Apolipoprotein(a) phenotype frequencies in patients with PVD did not differ from those of the control group. Both patients and controls with phenotype S2 had higher serum Lp(a) levels than those with phenotype S4. It should be emphasized that serum Lp(a) levels were significantly higher in PVD patients than controls for those with phenotype S2, S3/S4 and S4. Raised serum Lp(a) levels together with other lipoprotein abnormalities in patients with PVD imply a high cardiovascular risk. Genetic polymorphism clearly influences serum Lp(a) levels both in patients and controls. In patients with PVD, environmental and/or other genetic factors must play a role in raising Lp(a) levels.     

Incidence and progression of diabetic retinopathy among non-insulin-dependent diabetic subjects: a 4-year follow-up

BACKGROUND: To assess the incidence and progression of diabetic retinopathy and explore risk factors associated with them among non-insulin-dependent diabetes mellitus (NIDDM) patients. METHODS: A total of 471 NIDDM subjects aged > or 40 were recruited from four primary health care centres of northern Taiwan in 1986 and followed up for 4 years. Their ocular fundi were clearly visible by ophthalmoscopy and the status of diabetic retinopathy could be graded. A structured questionnaire interview was conducted to collect basic data. Overnight fasting venous blood was collected every year to measure the levels of glucose, glycosylated haemoglobin (HbA1c), cholesterol and high density lipoprotein cholesterol. RESULTS: Among the 344 subjects who had no retinopathy initially, 66 subjects developed retinopathy 4 years later giving a 4-year cumulative incidence of 19.2%. Of the 120 subjects initially with background or preproliferative retinopathy, evidence of deterioration developed in 36 subjects. The cumulative incidence of progression was 30%. Seven subjects developed proliferative retinopathy giving a cumulative incidence of progression to proliferative retinopathy of 5.8%. The univariate analysis disclosed that the development of retinopathy was correlated with mean fasting blood glucose (MFBG) and HbA1c, diabetic duration, diabetic treatment and residential area. The progression of retinopathy correlated with MFBG and proteinuria, and the progression to proliferative retinopathy correlated with MFBG. Stepwise logistic regression analysis revealed that MFBG and HbA1c were the significant risk factors related to the development of retinopathy. CONCLUSIONS: Diabetic control assessed by MFBG or HbA1c was the significant risk factor correlated with the incidence and progression of retinopathy.     

Lipid metabolism and renal protection by chronic cicletanine treatment in Dahl salt-sensitive rats with salt-induced hypertension

The role cardiac autonomic neuropathy (CAN) plays in diabetes is not well known. The aim of this study was to identify the factors involved in CAN in diabetic patients. One hundred patients, 44 insulin-dependent (IDDM) and 56 non-insulin-dependent (NIDDM), were investigated, using five standard tests. Three of these tests were for parasympathetic control (cardiac response to the lying-to-standing, deep breathing, and Valsalva tests), and the other two measured sympathetic control (testing for orthostatic hypotension and evaluating heart and blood pressure response to the handgrip test). Results were compared to those found in a series of 40 healthy volunteers. An age-adjusted comparison with the controls, showed that 34 patients had one abnormal parasympathetic test, 23 had two, and 6 patients had three. Cardiac parasympathetic neuropathy was thus present in 63% of the patients. The handgrip test was completed by 84 diabetic patients. There was evidence of orthostatic hypotension and/or an abnormal cardiac response to the handgrip in 15 of these patients, who all had a parasympathetic abnormality as well. There was no significant association between the type of diabetes and the presence of CAN. The duration of diabetes was significantly longer in patients with CAN (9.3 +/- 0.9 years) (p < 0.01) than in those with all three parasympathetic tests normal (5.8 +/- 0.9 years) (p < 0.01). The HbA1c level was also higher in patients with CAN than in those with three normal parasympathetic tests (9.95 +/- 0.35% versus 8.17 +/- 0.42%, p < 0.005). There was a significant association between the presence of retinopathy, observed by angiofluorography, and the presence of peripheral neuropathy confirmed by the electrophysiological investigation and the presence of CAN (p < 0.001). However, more than half the patients without retinopathy or nephropathy had CAN, and 11 of the 31 patients with a normal electrophysiological investigation also had CAN. Eighteen patients (6 IDDM) without retinopathy and nephropathy, who had been diabetic for less than 2 years, also had CAN. This study shows that CAN occurs early and is frequently found in a population of unselected diabetic patients. Metabolic factors may play an important role in its occurrence. CAN is significantly associated with the presence of retinopathy, which suggests that an impairment of autonomic peripheral blood flow control might be a contributing factor in the formation of microvascular lesions.     

Prevalence of retinopathy in people with diabetes, impaired glucose tolerance, and normal glucose tolerance

OBJECTIVE: Recently, an international expert committee published new revised criteria for diagnosing diabetes. According to the new criteria, the 2-h glucose level for diabetes in the oral glucose tolerance test (OGTT) is the same as in the previous World Health Organization criteria, but the cut point for the fasting blood glucose level has been lowered to be equivalent to the 2-h OGTT level. Measurement of the fasting blood glucose level is preferred to the 2-h OGTT glucose level. The ability of the new cut point for fasting blood glucose to discriminate between those at a high and a low risk for retinopathy was tested in a population-based study RESEARCH DESIGN AND METHODS: The population consisted of all the 1,008 subjects (456 men) born in 1935 and living in a Finnish city A screening for type 2 diabetes was carried out in the first phase. All participants who were not on antidiabetic medication were invited for an OGTT in the second phase. A fasting blood glucose value was measured from the diabetic subjects on antidiabetic medication. In addition, measurements of serum cholesterol, HDL cholesterol, and triglycerides were made, and fundus photographs were taken. Altogether, 831 subjects (368 men) (82%) participated and constitute the eligible study population for the present analyses. Fundus photographs were available for 790 subjects (347 men) (95%). RESULTS: There were 28 subjects (3.5%) who had mild retinopathic changes in the fundus photographs. Retinopathic changes were associated with higher fasting blood glucose levels, but not with any of the other background factors. The prevalence of retinopathy was 10.2% (95% CI 4.8-18.5) in subjects with a fasting blood glucose of > or =6.1 mmol/l, while it was 2.6% (1.5-4.0) in those with a lower fasting blood glucose level. In the former group, a majority (seven of nine) of the subjects with retinopathy were previously diagnosed diabetic patients. Some cases of retinopathy were found regardless the level of glycemia, and measurement of the 2-h OGTT glucose levels did not increase information. CONCLUSIONS: The results of this population study give support to the use of fasting blood glucose levels in diagnosing type 2 diabetes. The lower limit of the highest decile of the fasting glucose level was 6.1 mmol/l, and it discriminated subjects at a high risk for retinopathy from those at a low risk. Because of the limited number of subjects with retinopathy in this study, the level of hyperglycemia associated with retinopathy cannot be estimated accurately.