Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kojima Y, Furuyoshi N, Shichiri M
Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan.
Diabetes Res Clin Pract. 1995 May;28(2):103-17. doi: 10.1016/0168-8227(95)01064-k.
To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, we performed a prospective study of Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with multiple insulin injection treatment. A total of 110 patients with NIDDM was randomly assigned to multiple insulin injection treatment group (MIT group) or to conventional insulin injection treatment group (CIT group). Fifty-five NIDDM patients who showed no retinopathy and urinary albumin excretions < 30 mg/24 h at the baseline were evaluated in the primary-prevention cohort, and the other 55 NIDDM patients who showed simple retinopathy and urinary albumin excretions < 300 mg/24 h were evaluated in the secondary-intervention cohort. The appearance and the progression of retinopathy, nephropathy and neuropathy were evaluated every 6 months over a 6-year period. The worsening of complications in this study was defined as an increase of 2 or more steps in the 19 stages of the modified ETDRS interim scale for retinopathy and an increase of one or more steps in 3 stages (normoalbuminuria, microalbuminuria and albuminuria) for nephropathy. The cumulative percentages of the development and the progression in retinopathy after 6 years were 7.7% for the MIT group and 32.0% for the CIT group in the primary-prevention cohort (P = 0.039), and 19.2% for MIT group and 44.0% for CIT group in the secondary-intervention cohort (P = 0.049). The cumulative percentages of the development and the progression in nephropathy after 6 years were 7.7% for the MIT group and 28.0% for the CIT group in the primary-prevention cohort (P = 0.032), and 11.5% and 32.0%, respectively, for the MIT and CIT groups in the secondary-intervention cohort (P = 0.044). In neurological tests after 6 years, MIT group showed significant improvement in the nerve conduction velocities, while the CIT group showed significant deterioration in the median nerve conduction velocities and vibration threshold. Although both postural hypotension and the coefficient of variation of R-R interval tended to improve in the MIT group, they deteriorated in the CIT group. In conclusion, intensive glycemic control by multiple insulin injection therapy can delay the onset and the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese patients with NIDDM. From this study, the glycemic threshold to prevent the onset and the progression of diabetic microangiopathy is indicated as follows; HbA1c < 6.5%, FBG < 110 mg/dl, and 2-h post-prandial blood glucose concentration < 180 mg/dl.
为了研究强化血糖控制是否能降低糖尿病微血管并发症的发生频率或严重程度，我们对接受多次胰岛素注射治疗的日本非胰岛素依赖型糖尿病（NIDDM）患者进行了一项前瞻性研究。总共110例NIDDM患者被随机分配至多次胰岛素注射治疗组（MIT组）或传统胰岛素注射治疗组（CIT组）。55例在基线时无视网膜病变且尿白蛋白排泄量<30 mg/24 h的NIDDM患者在一级预防队列中接受评估，另外55例有单纯视网膜病变且尿白蛋白排泄量<300 mg/24 h的NIDDM患者在二级干预队列中接受评估。在6年期间，每6个月评估一次视网膜病变、肾病和神经病变的出现及进展情况。本研究中并发症的恶化定义为：视网膜病变改良ETDRS中期量表19个阶段中增加2个或更多阶段，肾病3个阶段（正常白蛋白尿、微量白蛋白尿和白蛋白尿）中增加1个或更多阶段。在一级预防队列中，6年后MIT组视网膜病变发生和进展的累积百分比为7.7%，CIT组为32.0%（P = 0.039）；在二级干预队列中，MIT组为19.2%，CIT组为44.0%（P = 0.049）。在一级预防队列中，6年后MIT组肾病发生和进展的累积百分比为7.7%，CIT组为28.0%（P = 0.032）；在二级干预队列中，MIT组和CIT组分别为11.5%和32.0%（P = 0.044）。在6年后的神经学检查中，MIT组神经传导速度有显著改善，而CIT组正中神经传导速度和振动阈值有显著恶化。虽然MIT组体位性低血压和R-R间期变异系数均有改善趋势，但CIT组却出现恶化。总之，多次胰岛素注射强化血糖控制可延缓日本NIDDM患者糖尿病视网膜病变、肾病和神经病变的发生及进展。从本研究来看，预防糖尿病微血管病变发生及进展的血糖阈值如下：糖化血红蛋白<6.5%，空腹血糖<110 mg/dl，餐后2小时血糖浓度<180 mg/dl。
