Slightly elevated blood pressure as well as poor metabolic control are risk factors for the progression of retinopathy in early-onset Japanese Type 2 diabetes

Not a few patients in Japan with early-onset type 2 (non-insulin-dependent) diabetes become blind due to proliferative diabetic retinopathy (PDR). However, the risk factors are poorly understood. The aim of this study was to determine the risk factors for background diabetic retinopathy (BDR) and PDR by following 394 Japanese patients with early-onset type 2 diabetes diagnosed before 30 years of age (mean age 27, mean blood pressure at entry 116/73 mm Hg). Of the 322 patients who were free of diabetic retinopathy at entry, 88 developed BDR, giving an incidence of 57.7 (95% CI 55.5-60. 0)/1000 person-years. Cox proportional hazard analysis revealed mean HbA(1c) and duration of diabetes to be significant predictors of development of BDR. Of the 160 patients with BDR, i.e., the 72 patients who had BDR at entry and the 88 who developed BDR during the follow-up, 50 developed PDR, giving an incidence of 17.9 (95% CI 13.6-23.6)/1000 person-years. Cox proportional hazard analysis indicated mean HbA(1c) and diastolic blood pressure to be significant predictors of the progression from BDR to PDR. In conclusion, in early-onset Japanese type 2 diabetic patients, the rates of both development of BDR and of progression from BDR to PDR appear to be potentially high. Not only lifetime exposure to glycemia but also a slightly elevated blood pressure level is an important risk factor for progression to PDR.     

High prevalence of proliferative retinopathy in diabetic patients with low pancreatic B-cell capacity

A retrospective study on the role of pancreatic B-cell insulin secretory capacity in the development of proliferative diabetic retinopathy was performed in 160 diabetic patients with a duration of diabetes of more than 10 years (mean 19.5 +/- 7.9 years). Pancreatic B-cell insulin secretory capacity was assessed in terms of the quantity of C-peptide excreted into urine per day (24-h urinary C-peptide). When the patients were divided into three groups according to the quantity of 24-h urinary C-peptide (group I, C-peptide less than 30 micrograms, n = 49; group II, 30 micrograms less than or equal to C-peptide less than 80 micrograms, n = 76; and group III, C-peptide greater than or equal to 80 micrograms, n = 35), the prevalence of proliferative diabetic retinopathy was much higher in group I (26.5%) than in group II (5.3%) or group III (2.9%). The incidence of proliferative diabetic retinopathy during the follow-up period (mean 9.8 +/- 4.8 years) was also highest in group I (20.0%, 2.7%, and 2.9% in groups I, II, and III, respectively). Other factors which might affect the development of proliferative diabetic retinopathy, including duration of diabetes and past glycemic control, were comparable in these three groups. In contrast, a division of the patients according to glycemic control revealed a strong correlation between glycemic control and background diabetic retinopathy whereas no such correlation was apparent with proliferative diabetic retinopathy. These data are consistent with the view that low pancreatic B-cell insulin secretory capacity may be a risk factor for the development of proliferative diabetic retinopathy.     

Association of plasma fibrinogen level and blood pressure with diabetic retinopathy, and renal complications associated with proliferative diabetic retinopathy, in Type 2 diabetes mellitus.

AIM: To clarify the association of several clinical parameters, including plasma fibrinogen level, with diabetic retinopathy in patients with Type 2 diabetes mellitus (DM). METHODS: A total of 294 Japanese patients with Type 2DM were studied; 53 patients with no diabetic retinopathy (NDR), 90 with background diabetic retinopathy (BDR), and 151 with proliferative diabetic retinopathy (PDR). Multiple logistic regression analysis was performed to assess variables independently associated with diabetic retinopathy in two settings: presence of retinopathy of any severity and presence of advanced retinopathy. RESULTS: The following parameters were identified as independent factors associated with the presence of diabetic retinopathy (NDR vs. BDR + PDR): type of therapy (P<0.0005), log-transformed plasma fibrinogen level (P < 0.05), mean blood pressure (P < 0.05), and duration of diabetes (P < 0.05). The independent variables associated with advanced retinopathy were type of therapy (P<0.00005), age (P<0.0005) and nephropathy (P<0.05). Body mass index, smoking and hypertensive status, HbA1c and total cholesterol levels were not independently associated. CONCLUSIONS: These data suggest that in patients with Type 2 DM, an increased blood viscosity due to high fibrinogen level as well as an elevated intravessel pressure play a role in the development of diabetic retinopathy, and that the progression to PDR is influenced or accompanied by the deterioration of renal status.     

The effect of residual beta-cell function on the development of diabetic retinopathy

The effect of residual B-cell function on retinopathy was evaluated in a cross-sectional study of 533 insulin-dependent diabetic patients (disease duration 0 to 45 years). One hundred and fifty-three patients with residual B-cell function, as evaluated by stimulated plasma C-peptide concentration, had lower prevalence of retinopathy than patients without B-cell function. The patients with B-cell function had a shorter duration of diabetes and were older at onset, but there was no difference in age at the time of the study. When patients with similar duration of diabetes were compared, no differences in the degrees of retinopathy could be demonstrated between patients with and without B-cell function. These results indicate that residual B-cell function does not protect against or delay the development of diabetic microvascular lesions.     

Insulin resistance and proliferative retinopathy: a cross-sectional, case-control study in 115 patients with type 2 diabetes

In this cross-sectional, case-control study we explored the association of proliferative diabetic retinopathy (PDR) with insulin resistance (IR) in type 2 diabetics with serum creatinine less than 2.0 mg/dl. For each PDR case, one reference case with background diabetic retinopathy (BDR) and two controls without retinopathy were identified. IR was evaluated by hyperinsulinemic euglycemic clamp; retinopathy was evaluated by indirect ophthalmoscopy and photography. Patients were matched by age, gender, and body mass index. PDR patients (n = 28) had higher IR and low-density lipoprotein cholesterol and triglyceride levels than BDR patients (n = 29), but comparable levels of glycosylated hemoglobin. Compared with patients without retinopathy (n = 58), those with PDR had higher IR, low-density lipoprotein cholesterol, and albuminuria (P < 0.05); those with BDR had higher glycosylated hemoglobin (P < 0.05), but comparable IR. At multivariate regression analysis, IR was the only independent marker of PDR among patients with retinopathy (P = 0.016). IR also retained its independent predictive value at multiple comparison among all groups (by Kruskal-Wallis test, P = 0.019). In type 2 diabetes, IR is an independent specific marker of proliferative retinopathy that may characterize patients at increased risk for blindness who may benefit most from early screening and therapeutic intervention. Longitudinal studies are needed to evaluate the role of IR in the pathogenesis of proliferative retinopathy.     

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

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

糖尿病微血管病变患者炎症因子水平、血浆同型半胱氨酸水平及血液流变学指标变化

目的 为探讨糖尿病视网膜病变严重程度与炎症因子、血浆同型半胱氨酸水平及血液流变学的关系.方法 完全随机选择2型糖尿病患者150例,按有无视网膜病变分为3组:糖尿病无视网膜病变组(NDR)48例、背景型糖尿病视网膜病变组(BDR)52例和增殖型糖尿病视网膜病变组(PDR)50例,检测3组病人的炎症因子、血浆同型半胱氨酸(Hcy)水平和血液流变学指标进行分析.结果 与糖尿病无视网膜病变组比较,背景型糖尿病视网膜病变组与增殖型糖尿病视网膜病变组的炎症因子、血浆Hcy水平、血液流变学指标明显升高,差异有统计学意义(P＜0.01);与背景型糖尿病视网膜病变组比较,增殖型糖尿病视网膜病变组的炎症因子、血浆Hcy水平、血液流变学指标明显升高,差异有统计学意义(P＜0.05).结论 炎症反应、高同型半胱氨酸血症及高粘血症参与了糖尿病视网膜病变的发生和发展过程.     

The frequency and severity of retinopathy are related to HbA1c values after, but not at, the diagnosis of NIDDM

OBJECTIVES: To examine the relationship between previous glycaemic exposure and prevalence of retinopathy 8 years after diagnosis of diabetes in 58 islet cell antibodies (ICA)-negative noninsulin-dependent diabetes mellitus (NIDDM) patients and in a group of 14 ICA-positive 'NIDDM' and insulin-dependent diabetes mellitus (IDDM) patients. DESIGN AND METHODS: The Wisconsin retinopathy scale was used to assess the retinopathy which was graded into mild, moderate and severe nonproliferative diabetic retinopathy (NPDR), or proliferative retinopathy (PDR). The frequency and severity of retinopathy was related to HbA1c levels at diagnosis, and 3 and 5 years later. RESULTS: Thirty of the 58 ICA-negative NIDDM patients (52%) but only 2 of the 14 ICA-positive 'NIDDM' or IDDM patients (14%) had mild-moderate-severe NPDR 8 years after diagnosis (P = 0.02). None had PDR. Retinopathy 8 years after diagnosis in NIDDM (= 58 ICA-negative patients) was correlated with the degree of glycaemic control (HbA1c levels) at 3 and 5 years after diagnosis, but not to HbA1c levels at diagnosis. The relative risk for a higher average HbA1c (per percentage) at 3 and 5 years was 1.56 for any retinopathy vs. no retinopathy (95% confidence interval 1.1-2.2; P = 0.01) and 1.68 for moderate to severe NPDR in comparison with no DR and mild NPDR (95% confidence interval 1.0-2.8; P = 0.04). CONCLUSIONS: Retinopathy after 8 years of diabetes in NIDDM patients was associated with impaired glycaemic control during previous years but not with glycaemic control at baseline. Good glycaemic control may prevent retinopathy in patients with NIDDM.     

Severity of diabetic retinopathy is linked to lipoprotein (a) in type 1 diabetic patients

To determine the relationship between plasma Lp(a) concentration and the risk of developing diabetic retinopathy, 341 Type 1 diabetic patients underwent an annual retinal fluorescein angiography and were assigned to one of 3 groups according to the stage of their diabetic retinopathy: no retinopathy (NR), non-proliferative diabetic retinopathy (N-PDR), or proliferative diabetic retinopathy (PDR). One hundred and twenty-three Type 1 diabetic patients had no retinopathy, 188 had N-PDR and 30 had PDR. The ages of the three groups and the duration of diabetes were significantly different. Hypertension, microalbuminuria and diabetic nephropathy were more frequent in PDR than in NR or N-PDR (p < 0.0001). Plasma HbA1c was higher in PDR than in NR or N-PDR (p < 0.01). Type 1 patients who had been diabetic for at least 20 years included 30 NR, 108 N-PDR and 24 PDR. Type 1 diabetic patients with PDR had microalbuminuria and macroproteinuria more frequently than other patients (p < 0.0001 and 0.01, respectively). Type 1 diabetic patients with PDR had the highest median plasma Lp(a) and the highest frequency of Lp(a) above 30 mg/dl (p < 0.05). Multivariate analysis carried out in Type 1 diabetic patients with a duration of diabetes of at least 20 years showed that microproteinuria, HbA1c and Lp(a) accounted significantly for 21% of variance in retinal status. Lp(a) above 30 mg/dl was related to the risk of developing PDR (OR = 8.40, p < 0.05). Lipoprotein(a) appears to be associated with the severity of diabetic retinopathy in Type 1 diabetic patients, and particular attention should be paid to those with Lp(a) above 30 mg/dl and pre-proliferative retinopathy.     

糖尿病视网膜病变与高同型半胱氨酸血症的关系

目的研究糖尿病视网膜病变与血浆同型半胱氨酸水平的关系。方法随机选择2型糖尿病患者120例,按有无视网膜病变分为3组：糖尿病无视网膜病变组(NDR)、背景型糖尿病视网膜病变组(BDR)和增殖型糖尿病视网膜病变组(PDR),检测3组患者的血浆同型半胱氨酸水平。结果BDR组与PDR组患者的Hcy水平明显高于NDR组(P＜0．01),PDR组的Hcy水平明显高于BDR组(P＜0．05),差异均有显著性意义(P＜0．05)。结论高同型丰胱氨酸血症不仅促进糖尿病视网膜病变的发生,而且与糖尿病视网膜病变的严重程度有关。     

糖尿病视网膜病变与血清Ⅳ型胶原和层粘连蛋白以及粘附分子变化的相关性

目的 探讨糖尿病视网膜病变不同时期细胞外间质、血管基膜成分以及血管内皮细胞粘附分子在血循环中的变化，了解他们与血管基膜和血管内皮细胞损伤的相关性。方法 85例(男40例、女45例)2型糖尿病患者分无视网膜病变(NDR)组31例、背景期视网膜病变(BDR)组24例和增殖期视网膜病变(PDR)组30例，采用放射免疫法和ELISA法测其血清Ⅳ型胶原(ⅣC)、层粘蛋白(LN)和血管内皮细胞粘附分子(sVCAM—1)含量，同时设健康体检者20人为对照组。结果 三组糖尿病患者血清LN、ⅣC、sVCAM—1水平均高于对照组。PDR组的血清LN、ⅣC和sVCAM—1水平与对照组比较，差异有非常显著意义(P＜0．01)，与NDR组比较，差异也有非常显著意义(P＜0．01)；BDR组血清LN、ⅣC和sVCAM—1水平与对照组比较，差异有非常显著意义(P＜0．01)；BDR组血清LN、ⅣC和sVCAM—1水平与对照组比较，差异有非常显著意义(P＜0．01)；PDR组与BDR组比较，仅LN、ⅣC差异有非常显著意义(P＜0．01)；BDR组与NDR组比较，仅sVCAM—1差异有显著意义(P＜0．05)。三组糖尿病患者血清三项指标之间无相关性(分别为r＝0．119，r＝0．167和r＝-0．210；P＞0．05)。结论 血清ⅣC、LN和sVCAM—1用于联合检测，能较好地反映糖尿病微血管病变的发展过程，为其早期诊断和治疗提供依据，也可作为糖尿病视网膜病变严重程度的估计和预后判断的指标。     

C-peptide secretion in calcific tropical pancreatic diabetes

Serum C-peptide levels were measured during a glucagon stimulation test in ten normal nonobese controls and 54 diabetic patients with recent onset of diabetes under 30 years of age. Diabetic patients were comprised of 13 CTPD, 23 IDDM, and 18 NIDDM. As similar to IDDM patients, serum C-peptide concentrations did not rise significantly (P greater than 0.05) in response to glucagon administration in CTPD-patients. Mean baseline and peak serum C-peptide concentrations in CTPD-patients were significantly lower (P less than 0.001) than the values in normal controls and NIDDM patients, but were significantly higher (P less than 0.05) than those in IDDM patients. We conclude that CTPD patients have partial C-peptide reserve, which may protect against ketosis and contribute to ketosis resistance in CTPD. Our results also suggest that CTPD patients require insulin treatment. Neither baseline nor peak C-peptide levels after glucagon could discriminate CTPD from IDDM and CTPD from NIDDM.     

High levels of erythrocyte aldose reductase and diabetic retinopathy in NIDDM patients

Summary Erythrocyte aldose reductase was determined in 90 NIDDM patients by a two-site ELISA using recombinant human aldose reductase. The level of aldose reductase did not correlate with age, duration of diabetes, fasting blood glucose and HbA_1cof the patients. Among 38 patients with diabetes for more than 10 years, aldose reductase in those with retinopathy (including non-proliferative and proliferative) was significantly higher than in those without, while no difference in the means of the average HbA_1c, maximum and minimum blood pressure levels was observed between the two groups. The results indicate that the level of aldose reductase in the erythrocyte of diabetic patients is associated with the presence of retinopathy.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - IDDM insulin-dependent diabetes mellitus     

Retinopathy in older patients with diabetes mellitus

PURPOSE: We studied the effects of the age and/or disease duration in diabetics on the progression of diabetic retinopathy (DR). METHODS: The population consisted of 3614 type 2 diabetes mellitus (DM) patients. The subjects were divided into three age groups (elderly, > or = 65 years old; middle-aged, 64-40 years old, and younger < 40 years old) for disease duration-adjusted comparison with and without DR and proliferative diabetic retinopathy (PDR). Then, in 503 patients with 8-year follow-up data available, the frequency of development/progression of DR and the rate of progression to PDR were compared among the three groups. Thirdly, in the elderly patients, DR prevalence and the frequency of the development/progression of DR were compared between two groups with different diabetes duration (> or = 6 years and < or = 5 years). RESULTS: The prevalence of DR increased significantly with age (P < 0.001). The prevalence of PDR decreased significantly with age (P < 0.001). The overall frequency of the development and/or progression of DR increased significantly with age (P = 0.002); however, age was not related to the frequency of progression to PDR. In the patients with diabetes duration of 6-15 years, the frequency of the development/progression of DR and of progression to PDR after an 8-year follow up tended to decrease with age. Elderly patients with a diabetes duration of > or = 6 years showed significantly higher rate of prevalence of DR and frequency of development/progression of DR in an 8-year period than those with diabetes of a shorter duration (P < 0.001 and P < 0.001, respectively). CONCLUSION: In elderly DM patients, the prevalence of DR was increased even in the short duration and development/progression rates of DR were increased, while the relative frequency of PDR was decreased. Older-onset DM patients appear to be at a lower risk for progression to PDR.     

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

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

Limited joint mobility (LJM) of the hand in patients with diabetes mellitus: relation to chronic complications.

Limited joint mobility (LJM) of the hand was studied by visual examination in 361 diabetic outpatients aged 11 to 83 years, and 45 non-diabetic controls, without evidence of arthritis. LJM was evident in 58% of diabetic subjects and 4% of controls (p less than 0.001). LJM was noted in 131 (55%) of the 238 patients with insulin-dependent diabetes mellitus (IDDM) as opposed to 31 of the 41 patients (76%) with non-insulin-dependent diabetes mellitus (NIDDM). LJM occurred in 60 of the 82 diabetic subjects (73%) receiving insulin therapy who developed diabetes after the age of 35 years. LJM was significantly related to duration of diabetes in the patients with IDDM less than 40 years of age but was not associated with duration in the patients with NIDDM. A significant association of LJM and neuropathy was noted in patients less than 40 years of age with less than 20 years of diabetes. A significant association of LJM and retinopathy was also noted in those less than 40 years of age with less than 30 years of diabetes. There was no association of LJM and nephropathy regardless of age or duration of diabetes.     

Heart rate elevation and diabetic retinopathy in patients with type 2 diabetes mellitus and normoalbuminuria

To investigate the role of heart rate (HR) and blood pressure (BP) for diabetic retinopathy, 24-h ambulatory HR and BP were monitored for 162 in patients with type 2 diabetes and normoalbuminuria. The fundus was assessed as no retinopathy, simple diabetic retinopathy (SDR) and proliferative retinopathy (PDR). Comparing the highest with the lowest quartile of diabetic duration, the relative risk for retinopathy was 9.3 and for nocturnal HR, it was 3.6. Comparison among three retinopathy groups (no retinopathy, group 1, n=122; SDR, group 2, n=24; Pre-PDR or PDR, group 3, n=16) showed that 24-h and nocturnal HR were significantly higher in group 3 (80+/-9 and 71+/-9 beats per min) than in group 2 (73+/-8 and 64+/-8) and group 1 (72+/-7 and 60+/-7). In multiple logistic analysis, the odds ratio of diabetic duration and nocturnal HR to the existence of retinopathy was 1.17 (95% CI, 1.10-1.25, P=0.00001) and 1.11 (95% CI, 1.05-1.17, P=0.0002). We concluded that diabetic retinopathy is related to diabetic duration and high heart rate in type 2 diabetes mellitus with normoalbuminuria. Heart rate elevation may be a predictor of advanced retinopathy.     

Pulmonary diffusing capacity, serum angiotensin-converting enzyme activity and the angiotensin-converting enzyme gene in Japanese non-insulin-dependent diabetes mellitus patients.

We investigated the independent change in pulmonary diffusing capacity (DLCO) as one manifestation of pulmonary microangiopathy and to analyze the correlation between DLCO and serum ACE. We also examined the association between DLCO and the ACE genes. We examined pulmonary functions, especially %DLCO/VA (DLCO corrected by alveolar volume, percent predicted) in 54 NIDDM patients and 34 age-matched normal control subjects. Subjects were subdivided according to the degree of retinopathy. Serum ACE level was assayed by a colorimetric method in 54 patients and an insertion/deletion polymorphism in the ACE gene was amplified using the polymerase chain reaction in 52 of the 54 patients. There was a significant reduction of %DLCO/VA (percent predicted P < 0.05) in diabetic patients. In the proliferative retinopathy (PDR) group. %DLCO/VA was significantly (P < 0.05) lower than in the no diabetic retinopathy (NDR) and simple diabetic retinopathy (SDR) groups. Although the levels of serum ACE were within normal ranges in all diabetic groups, %DLCO/VA was negatively correlated with serum ACE values (r = 0.49, P < 0.0002, y = -1.4x + 109.3). Differences among DD, ID and II type of the ACE gene, with respect to the incidence of abnormal values of each clinical parameter, were not significant. DLCO was significantly reduced in patients with PDR and the serum ACE was significantly related to impaired DLCO. Our study suggests the existence of microangiopathic involvement of pulmonary vessels in NIDDM patients.     

血浆同型半胱氨酸浓度与2型糖尿病视网膜病变的关系

目的　观察空腹血浆总同型半胱氨酸 (Hcy)水平与 2型糖尿病视网膜病变发生发展的关系。方法　研究对象为 5 5例 2型糖尿病 (DM)和 19例 (男 12例 ,女 7例 )非DM健康对照者 (CON)。DM组分为两个亚组 :无微血管并发症 (NDC)组 39例 (男 17例 ,女 2 2例 ) ,糖尿病视网膜病变 (DR)组16例 (男 8例 ,女 8例 )。所有患者肾功能和尿白蛋白 /肌酐 (Alb/Cr)均正常。根据眼底荧光造影判断视网膜病变的严重程度。应用高效液相 反相色谱分析和荧光检测的方法测定空腹血浆总Hcy水平。结果　DR组、NDC组和CON组间的血浆总Hcy浓度差异有显著性 (F =2 4 0 5 ,P =0 0 31) ,DR组血浆总Hcy水平 [(14 7± 5 2 8) μmol/L]显著高于NDC组 [(11 3± 4 94) μmol/L]和CON组 [(9 6 5± 2 6 6 )μmol/L]。NDC组与CON组比较差异无显著性。在DR组 ,增殖性视网膜病变 (PDR)亚组总Hcy水平显著高于背景性视网膜病变 (BDR)亚组 (t=2 4 0 5 ,P =0 0 31)。本研究中 ,总Hcy超过 14 97μmol/L即为高同型半胱氨酸血症 ,其中PDR亚组有 4例 ,BDR亚组为 1例。结论　伴视网膜病变的 2型DM患者血浆总Hcy水平高于正常人 ,其中PDR组的血浆总Hcy浓度高于BDR组。空腹血浆同型半胱氨酸水平可能是 2型糖尿病视网膜病变的重要危险因素之一。     

Duration of residual B-cell function in maturity-onset diabetes

Summary In order to evaluate factors influencing the duration of residual B-cell function in maturityonset diabetics we investigated 104 patients (age 60±11 years) with a mean duration of disease of 11.3±8.7 years by measuring fasting C-peptide (FCP) and fasting blood glucose levels (FBG), C-peptide increment after a standardized breakfast and both mean diurnal plasma glucose (MBG) and mean diurnal C-peptide levels (MCP). C-peptide levels were found to be reciprocally dependent on both the age at onset (positively) and, conversely, on the duration of diabetes (y=0.75+0.026x₁−0.049x₂; R=0.52, t₁=2.76, t₂=−4.08). In particular, the present B-cell secretory capacity appears to be lower the younger the patients were at onset, thus suggesting that inherent impairment of B-cell capacity may play a crucial role in determining age at onset of type II diabetes and thus the duration of their residual B-cell function. Moreover, by analyzing separately the data from patients treated with insulin and oral agents respectively, we found that the influence of the duration of the disease on the rate on B-cell exhaustion is unrelated to the mode of treatment even though B-cell capacity at onset appears to be more severely reduced in insulin-treated subjects who, apart from anything else, were younger at onset. In addition, no significant difference was found in FCP levels between patients showing MBG values above or below 160 mg/dl (1.76±0.66vs 1.57±0.68 ng/ml), whereas MCP values were lower in patients with MBG above 160 mg/dl (2.14±0.92vs 2.55±0.88 ng/ml; p<0.05) who, on the other hand, showed significant reduction in the C-peptide response to breakfast. These data suggest that prolonged metabolic derangement may impair the physiological response of B-cells and eventually lead, via B-cell overstimulation, or via a gap between synthesis and release of insulin, or through other as yet poorly understood mechanisms, to earlier insulin dependence in maturity-onset diabetic patients. This work was partially supported by C.N.R. grant N. 82.02146.04