Increased urinary levels of CXCL5, CXCL8 and CXCL9 in patients with Type 2 diabetic nephropathy.

CXC chemokines are particularly significant for leukocyte infiltration in inflammatory diseases. Recent reports have shown that inflammation is one of potential pathogenic mechanisms for diabetic nephropathy. However, information on inflammation related with CXC chemokines in human Type 2 diabetic nephropathy still remains scarce. We measured urinary and serum levels of three CXC chemokines, CXCL5, CXCL8 and CXCL9, in 45 Type 2 diabetic patients (DM), 42 primary renal disease (PRD) patients and 22 healthy controls by enzyme-linked immunosorbent assay. Urinary levels of CXCL5, CXCL8 and CXCL9 in DM were significantly elevated compared to those in controls (P<.0001, P<.01, P<.001; respectively). They increased consistent with urinary albumin excretion rate (UAER) and correlated with UAER in partial correlation analyses (r=0.41, P<.01; r=0.40, P<.01; r=0.45, P<.01; respectively). Urinary levels of CXCL5 in DM were significantly interrelated to HbA(1c) (r=0.42, P<.01). On the other hand, PRD showed significant increased levels of urinary CXCL8 and CXCL9 compared to controls (P<.001, P<.01; respectively), and so did PRD as UAER increased. However, there were no significant elevations of urinary levels of CXCL5 in PRD in spite of the increased UAER. We found significant associations of UAER in DM with diabetes duration, 1/serum creatinine, urinary CXCL5 (adjusted R(2)=0.67, P<.0001) or CXCL9 (adjusted R(2)=0.69, P<.0001) in a stepwise multiple regression analysis. These results suggest that these three CXC chemokines may be involved in the progression of human Type 2 diabetic nephropathy and that CXCL5 may be of use for telling diabetic nephropathy from primary renal diseases.

Effects of weight loss in obese subjects with normal fasting plasma glucose or impaired glucose tolerance on insulin release and insulin resistance according to a minimal model analysis.

We investigated effects of weight loss from diet and exercise regimen in obese subjects with normal fasting plasma glucose or impaired glucose tolerance (IGT) on insulin release capacity and insulin sensitivity. Eight subjects were recruited among visceral obesity patients (4 men, 4 women; age range, 24 to 57 years; body mass index [BMI], 32.8 to 60.3 kg/m(2)). All were admitted to Chiba University Hospital for 2 weeks, were treated with a tapering 5,023 to 2,930 kJ diet, and were given exercise equivalent to 628 kJ/d. For assessments, we used a combination of C-peptide secretion rate determination and minimal model analysis as previously reported. BMI and visceral fat area (V) significantly decreased (BMI on initiation v after intervention, 43.0 +/- 3.2 v 40.3 +/- 3.1 kg/m(2), P <.05; V, 224 +/- 22 v 188 +/- 22 cm(2); P <.05). Fasting immunoreactive insulin (F-IRI) and leptin concentrations decreased significantly. Capacity for insulin release in response to glucose increased in all subjects (first-phase insulin secretion [CS1], 4.66 +/- 4.05 v 6.81 +/- 4.57 ng/mL/5 min, P <.05), but the insulin sensitivity index (S(i)) did not change significantly. These data suggest that weight reduction early in development of type 2 diabetes can oppose progression of diabetes by improving capacity for insulin release.

Topical treatment with 22-oxacalcitriol (OCT), a new vitamin D analogue, caused severe hypercalcemia with exacerbation of chronic renal failure in a psoriatic patient with diabetic nephropathy; a case report and analysis of the potential for hypercalcemia.

Vitamin D has been used for topical treatment of psoriasis, and 22-oxacalcitriol (OCT), shown to be less calcemic, was developed for the topical treatment of psoriasis in Japan. Recently, we treated a psoriatic patient with diabetic nephropathy who developed severe hypercalcemia with exacerbation of chronic renal failure by the use of topical OCT. Analysis of the reported cases demonstrated that both the severity of psoriasis and renal dysfunction are critical factors in the induction of hypercalcemia in the topical treatment of psoriasis. Therefore, we must pay attention to the severity of psoriasis, especially when complicated by renal function impairment. Regular monitoring of Ca and renal function is essential to avoid life-threatening hypercalcemia from the topical treatment with vitamin D analogues.