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When given in addition to a RAS inhibitor, finerenone reduced albuminuria without adverse effects on serum potassium levels or renal function in Japanese patients with T2DM and DN.

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OBJECTIVE -The present study was conducted to investigate the effect of an aldose reductase inhibitor, epalrestat, on autonomic and somatic neuropathy at an early stage in type 2 diabetic patients by assessing the pupillary light reflex and minimum latency of the F-wave. RESEARCH DESIGN AND METHODS-A total of 30 diabetic patients with subclinical or mild diabetic neuropathy were randomly allocated to a control group (n ϭ 15) and epalrestat (150 mg/day) group (n ϭ 15). After 24 weeks, the pupillary light reflex test, cardiovascular autonomic function tests, and nerve conduction study were performed.RESULTS -The beneficial effect of epalrestat on the pupillary light reflex was observed in the minimum diameter after light stimuli (P ϭ 0.044), constriction ratio (P ϭ 0.014), and maximum velocity of constriction (P ϭ 0.008). Among cardiovascular autonomic nerve functions, the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing was significantly improved by epalrestat (P ϭ 0.037). Minimum latencies of F-wave of median and tibial motor nerves were significantly shortened by epalrestat (P ϭ 0.002 and P ϭ 0.001, respectively); however, no significant effects were observed in motor or sensory nerve conduction velocity.CONCLUSIONS -These observations suggest that epalrestat may have therapeutic value at the early stage of diabetic neuropathy and that the pupillary light reflex and minimum latency of F-wave may be useful indicators of diabetic neuropathy. Diabetes Care 24:1093-1098, 2001D iabetic neuropathy is generally classified into somatic and autonomic neuropathy. Although somatic neuropathy can be characterized by symptoms such as numbness, paresthesia, and abnormal sensation, the symptoms of autonomic neuropathy do not appear until the advanced stage.Diabetic autonomic neuropathy causes functional disorders of many organs, such as cardiovascular, gastrointestinal, genitourinary, metabolic, and pupillary dysfunctions. Among these, cardiovascular autonomic neuropathy may increase the risk of sudden death and affects the mortality of diabetic patients (1,2). Therefore, the diagnosis and treatment of autonomic neuropathy at an early stage is important for the management of diabetic patients.It is well known that diabetic autonomic neuropathy develops within a short duration of diabetes even when somatic neuropathy is not apparent (3,4). Furthermore, the abnormalities in pupillary functions can be detected earlier than those in cardiovascular autonomic functions and are considered the earliest signs of diabetic autonomic neuropathy (5-10). Therefore, the pupillary light reflex test has been used for evaluating diabetic autonomic neuropathy.It has been demonstrated that strict glycemic control can decrease the incidence of diabetic complications, including autonomic neuropathy (11). However, it is impossible to completely prevent the development of diabetic complications by glycemic control alone, except by performing a pancreas transplantation. Therefore, different t...

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Macrovascular complications such as myocardial infarction, angina pectoris and cerebrovascular accidents are the major causes of mortality in diabetic patients [1,2]. Although the maintenance of a good glycaemic control for a long period can decrease the risk of the development of diabetic microangiopathy [3], the development of diabetic macroangiopathy cannot be prevented by glycaemic control [3,4]. Therefore, it is very important to establish the pathogenesis of diabetic macroangiopathy.Various hypotheses including increased polyol pathway activity, protein kinase C (PKC) activation, increased oxidative stress and enhanced non-enzymatic glycation have been implicated in the pathogenesis of diabetic microangiopathy such as retinopathy, nephropathy and neuropathy [5,6]. Hyperglycaemia-induced metabolic alterations could also contribute to the development of diabetic macroangiopathy. Although the importance of the latter three metabolic deficits in the pathogenesis of diabetic macroangiopathy have been investigated precisely [7±12], the relation between polyol pathway hyperactivity and diabetic macroangiopathy remains unclear. Diabetologia (1999) Abstract Aims/hypothesis. Although increased polyol pathway activity has been implicated in the pathogenesis of diabetic microangiopathy, the relation with diabetic macroangiopathy remains unclear. Galactose feeding is known to stimulate the polyol pathway and to develop abnormalites similar to those in diabetic microangiopathy. Our study was conducted to investigate whether an activation of polyol pathway by long-term treatment with galactose produced morphological changes in coronary arteries of dogs and the effect of an aldose reductase inhibitor, epalrestat, was also studied. Methods. Dogs received either normal chow or chow containing 30 % galactose with or without epalrestat given orally (20 or 50 mg × kg ±1 ). After 44 months, morphometric analyses of coronary arteries were carried out and the galactitol contents in aortas were measured.Results. The ratio of areas of the intimal layer to those of the medial layer, an indicator of intimal thickening, was statistically significantly increased in galactosefed dogs compared with control dogs. Galactose-fed dogs had a remarkable accumulation of galactitol in their aortas. These morphological and biochemical deficits were reduced by treatment with epalrestat. Conclusion/interpretation. This report morphologically shows diabetes-like macrovascular abnormalities in galactosaemic animals, suggesting that polyol pathway hyperactivity is closely related to the development of diabetic macroangiopathy, which could be prevented by aldose reductase inhibition. [Diabetologia (1999

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