Baba T, Neugebauer S, Watanabe T
Dohtai Clinic Kajiwara, Kamakura, Japan.
Drugs. 1997 Aug;54(2):197-234. doi: 10.2165/00003495-199754020-00002.
Hypertension and diabetes mellitus are common chronic conditions which frequently coexist. Diabetic nephropathy is a major cause of elevated blood pressure in patients with insulin-dependent diabetes mellitus (IDDM). Diabetic nephropathy, arterial sclerosis, obesity and association of essential hypertension can be the causes of hypertension in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ambulatory blood pressure monitoring has revealed that the nocturnal fall of blood pressure is blunted in patients with diabetic nephropathy. A blunted diurnal blood pressure variation is seen in microalbuminuric diabetic patients and even in some normoalbuminuric patients. Accumulating data suggest that normalisation of blood pressure in hypertensive IDDM patients is most important to minimise the loss of kidney function. Angiotensin converting enzyme (ACE) inhibitors have been reported to be effective in postponing the development of nephropathy and in slowing its progression. Whether only ACE inhibitors have such beneficial renal effects on diabetic nephropathy is under discussion. While many studies have suggested that insulin resistance and hyperinsulinaemia are related to an elevated blood pressure in hypertensive patients, there does not seem to be enough evidence to prove that insulin per se can raise blood pressure in humans. Neither an insulin infusion within a physiological range nor sustained hyperinsulinaemia and insulin resistance (e.g. patients with insulinoma, cystic ovary syndrome) have been associated with an elevated blood pressure. Insulin resistance in some hypertensive patients may be a consequence of a decreased blood flow due to an increased peripheral resistance. Preliminary evidence suggests that low birth weight or impaired fetal growth is related to hypertension and NIDDM. Familial clustering of diabetic nephropathy suggests the contribution of genetic susceptibility and/or environmental inheritance. The frequent association of nephropathy with hypertension has led to research on the genes related to hypertension (ACE, angiotensinogen). Nevertheless, to date no reliable and clinically useful genetic marker has been found. Attempts to correct the metabolic abnormalities derived from diabetes are a new topic in the treatment of diabetic nephropathy. The effects of HMG CoA reductase inhibitors (antihypercholesterolaemic drugs), aldose reductase inhibitors (inhibitors of the polyol pathway) and glycation inhibitors (inhibitors of formation of advanced glycosylation end-products) on diabetic nephropathy have been evaluated in animal studies and in some clinical trials. Thus far, results with HMG CoA reductase and aldose reductase inhibitors have been somewhat conflicting. The potential therapeutic role of glycation inhibition in the treatment of diabetes deserves further study.
高血压和糖尿病是常见的慢性疾病，常同时存在。糖尿病肾病是胰岛素依赖型糖尿病（IDDM）患者血压升高的主要原因。糖尿病肾病、动脉硬化、肥胖以及原发性高血压的关联可能是非胰岛素依赖型糖尿病（NIDDM）患者高血压的病因。动态血压监测显示，糖尿病肾病患者夜间血压下降减弱。微量白蛋白尿糖尿病患者甚至一些正常白蛋白尿患者存在昼夜血压变化减弱的情况。越来越多的数据表明，高血压IDDM患者血压正常化对于将肾功能损失降至最低最为重要。据报道，血管紧张素转换酶（ACE）抑制剂在延缓肾病发展和减缓其进展方面有效。关于是否只有ACE抑制剂对糖尿病肾病具有这种有益的肾脏作用仍在讨论中。虽然许多研究表明胰岛素抵抗和高胰岛素血症与高血压患者的血压升高有关，但似乎没有足够的证据证明胰岛素本身能使人类血压升高。无论是生理范围内的胰岛素输注，还是持续性高胰岛素血症和胰岛素抵抗（如胰岛素瘤、多囊卵巢综合征患者）都与血压升高无关。一些高血压患者的胰岛素抵抗可能是外周阻力增加导致血流减少的结果。初步证据表明，低出生体重或胎儿生长受限与高血压和NIDDM有关。糖尿病肾病的家族聚集表明遗传易感性和/或环境遗传的作用。肾病与高血压的频繁关联引发了对与高血压相关基因（ACE、血管紧张素原）的研究。然而，迄今为止尚未发现可靠且临床有用的基因标记。纠正糖尿病引起的代谢异常是糖尿病肾病治疗中的一个新课题。HMG CoA还原酶抑制剂（抗高胆固醇血症药物）、醛糖还原酶抑制剂（多元醇途径抑制剂）和糖基化抑制剂（晚期糖基化终产物形成抑制剂）对糖尿病肾病的影响已在动物研究和一些临床试验中进行了评估。到目前为止，HMG CoA还原酶和醛糖还原酶抑制剂的结果有些相互矛盾。糖基化抑制在糖尿病治疗中的潜在治疗作用值得进一步研究。
