The Clinical Characteristics of Normoalbuminuric Renal Insufficiency in Korean Type 2 Diabetic Patients: A Possible Early Stage Renal Complication

It has been recently reported that a considerable portion of diabetic patients with renal insufficiency show normoalbuminuria. As little is known about normoalbuminuric renal insufficiency in the Asian population, we examined its prevalence and clinical characteristics in Korean type 2 diabetic patients. We studied 562 patients with type 2 diabetes from Seoul National University Hospital. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula and the degree of albuminuria was evaluated by spot urine albumin-creatinine ratio. Of 562 patients, 151 (26.9%) patients had renal insufficiency (eGFR <60 mL/min/ 1.73m(2)). Among them, 44 (29.1%) patients had normoalbuminuria. After excluding the patients using renin-angiotensin system (RAS) inhibitors, the prevalence of normoalbuminuric renal insufficiency was 35.3% (18 of 51 patients). Compared with microand macroalbuminuric renal insufficiency, normoalbuminuric renal insufficiency was associated with the female predominance, shorter duration of diabetes, lower prevalence of diabetic retinopathy, and lower prevalence of using antihypertensive drugs except RAS inhibitors. The prevalence decreased progressively with an increase in the duration of diabetes and an increase in the severity of retinopathy. Normoalbuminuric renal insufficiency was prevalent in Korean type 2 diabetic patients. The association with a shorter duration of the diabetes and a lower prevalence of retinopathy suggests that it might be an early stage renal complication.

Interaction of Pituitary Adenylate Cyclase-Activating Polypeptide and Angiotensin II on Aldosterone Production in Human Adrenocortical H295R Cells / 대한내분비학회지

BACKGROUND: Evidence is accumulating that aldosterone secretion can be regulated in a paracrine and/or an autocrine manner by several neuropeptides locally released within the adrenal gland. Among neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) is present in high concentration in the human adrenal gland. The purpose of this study was to investigate the action of PACAP and the interaction between PACAP and angiotensin II (AII), the main physiologic aldosterone secretagogue, in aldosterone production in human H295R adrenocortical cells. METHODS: H295R cells were incubated with increasing concentrations of PACAP (10(-11)M~10(-7)M) in the absence or presence of 10(-7)M AII. Aldosterone concentration in the supernatant was determined by RIA. Intracellular cAMP content was measured by RIA and total inositol phosphate (IP) production by anion exchange chromatography. Gene expression of CYP11B2 was studied by RT-PCR. RESULTS: In H295R cells, PACAP stimulated aldosterone production in a dose-dependent manner. Incubation of H295R cells with PACAP in the presence of AII significantly increased aldosterone production, compared with that of PACAP alone. PACAP dose-dependently increased cAMP production, but 10(-7)M AII had no effect on either basal or PACAP-stimulated cAMP production. Total IP production was not affected by PACAP, but was increased by 10(-7)M AII; an increase that was not further increased by addition of PACAP. RT-PCR analysis of H295R cells which were exposed to 10-7M PACAP or 10(-7)M AII showed an increase in CYP11B2 transcript signal. Induction of CYP11B2 mRNA expression in response to treatment with both PACAP and AII was significantly more than that resulting from using PACAP alone. CONCLUSION: The present study demonstrates that PACAP exerts a direct stimulatory effect on aldosterone production through induction of CYP11B2 mRNA expression by adenylate cyclase activation as the main intracellular signal pathway in H295R cells. Furthermore, there may be some additive effects between PACAP and AII on aldosterone production.