OBJECTIVEUrinary liver-type fatty acid-binding protein (u-LFABP) is a marker of tubulointerstitial inflammation and has been shown to be increased in patients with type 1 diabetes and is further increased in patients who progress to micro- and macroalbuminuria. Our aim was to evaluate u-LFABP as a predictor of progression to micro- and macroalbuminuria in type 1 diabetes.RESEARCH DESIGN AND METHODSFrom an inception cohort of 277 patients, u-LFABP, adjusted for urinary creatinine (enzyme-linked immunosorbent assay), was measured in 24-h urine samples from 165 normoalbuminuric patients 9.6 ± 3.5 (mean ±SD) years after onset of type 1 diabetes. The outcome measured was development of persistent micro- or macroalbuminuria or death.RESULTSPatients were followed for a median of 18 (range 1–19) years; 39 progressed to microalbuminuria, 8 of those progressed further to macroalbuminuria, and 24 died. In a Cox regression model, baseline log u-LFABP levels predicted the development of microalbuminuria, adjusted for known risk factors (sex, age, A1C, systolic and diastolic blood pressure, albumin excretion rate, serum creatinine, and smoking) (hazard ratio [HR] 2.3 [95% CI 1.1–4.6]) and log u-LFABP predicted mortality (adjusted HR 3.0 [1.3–7.0]). u-LFABP (above versus below the median) predicted the development of macroalbuminuria (adjusted HR 2.6 [1.2–5.4]). As a continuous variable, u-LFABP tended to predict macroalbuminuria (HR 1.9, P = 0.2), but numbers were small.CONCLUSIONSHigh levels of the tubular inflammation marker u-LFABP predict the initiation and progression to diabetic nephropathy and all-cause mortality, independent of urinary albumin excretion rate and other established risk factors.

OBJECTIVEWe studied tubular and glomerular damage in type 1 diabetic patients by measuring urinary–liver fatty acid binding protein (U-LFABP) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on U-LFABP in patients with diabetic nephropathy.RESEARCH DESIGN AND METHODSWe studied Caucasians with type 1 diabetes: 58 with normoalbuminuria (urinary albumin <30 mg/24 h), 45 with persistent microalbuminuria (30–300 mg/24 h), and 45 with persistent macroalbuminuria (≥300 mg/24 h). A control group consisted of 57 healthy individuals. The groups were matched by sex and duration of diabetes. In addition, U-LFABP was measured in 48 type 1 diabetic patients with diabetic nephropathy in a randomized crossover trial consisting of 2 months of treatment with 20, 40, and 60 mg lisinopril once daily in random order.RESULTSIn the cross-sectional study, levels of U-LFABP were significantly higher in normoalbuminuric patients versus those in the control group (median 2.6 [interquartile range 1.3–4.1] vs. 19 [0.8–3.0] μg/g creatinine, P = 0.02) and increased with increasing levels of albuminuria (microalbuminuric group 4.2 [1.8–8.3] μg/g creatinine and nephropathy group 71.2 [8.1–123.4], P < 0.05 for all comparisons). U-LFABP correlates with the urinary albumin-to-creatinine ratio (R2 = 0.54, P < 0.001). In the intervention study, all doses of lisinopril significantly reduced urinary albumin excretion rate and U-LFABP from baseline. The reductions in U-LFABP were 43, 46, and 40% with increasing doses of lisinopril (NS).CONCLUSIONSAn early and progressive increase in tubulointerstitial damage as reflected by increased U-LFABP levels occurs in type 1 diabetic patients and is associated with albuminuria. Furthermore, ACE inhibition reduces the tubular and glomerular damage and dysfunction.

Animal studies have demonstrated lower levels of 1,25(OH)2D3 in a type 2 diabetes model compared with controls (1). Alterations in circulating vitamin D3 metabolites, such as decreased 1␣-hydroxylase activity and enhanced renal 25-hydroxylase activity, have been found in both experimental and human diabetes. These alterations in vitamin D metabolism may be associated with the deranged mineral homeostasis and skeletal morphology observed in rats and people with chronic insulin deficiency (2). Experimentally, vitamin D deficiency progressively reduces insulin secretion, and this reduction soon becomes irreversible (3). It was also shown that insulin deficiency may be associated with lower vitamin D-binding protein and 1,25(OH)2D3 serum levels in rats. These decreases are somewhat dependent on androgen concentration, but they are counteracted by estrogens (4).Several studies have demonstrated abnormalities in calcium, phosphate, and vitamin D metabolism in diabetic patients. In particular, Pietschmann et al. (5) evaluated 25(OH)D levels in type 1 and type 2 diabetic patients and found no difference in 25(OH)D levels between type 1 diabetic patients and control subjects, whereas 25(OH)D levels were significantly decreased in type 2 diabetic patients (5).We conducted an observational study in 799 ambulatory postmenopausal Italian women in order to assess the prevalence of hypovitaminosis D and dietary calcium insufficiency. In all patients, the levels of 25(OH)D3 (obtained by radioimmunoassay method with double antibody provided by DiaSorin), calcium intake (obtained by a questionnaire filled in by a general practitioner), and several Activity Daily Living (ADL) criteria were assessed. The samples were collected in February and March 2000.We identified 66 type 2 diabetic patients based on medical history. Female patients and control subjects were comparable for age and years since menopause, but BMI was significantly higher in diabetic patients. The ADL score was significantly worse in diabetic patients than in control subjects (P Ͻ 0.01). The 25(OH)D levels (means Ϯ SD) were significantly lower in diabetic patients than in control subjects (11 Ϯ 9.8 vs. 9 Ϯ 11.3 ng/ml, P Ͻ 0.008), and the prevalence of 25(OH) deficiency (Ͻ5 ng/ml) was significantly higher in diabetic patients than in control subjects (39 vs. 25%). Dietary calcium intake was significantly lower in diabetic patients than in control subjects (792.9 Ϯ 400.9 vs. 679 Ϯ 316.9 mg/day, P Ͻ 0.020). The significance of these findings remains unclear. The general recommendation for overweight diabetic patients to lower fat dairy product consumption may explain the lower calcium intake. We have no data that might explain the higher prevalence of hypovitaminosis D among diabetic patients. We believe our results will lead to additional studies on the hypothetical circular relationship among diabetes, vitamin D repletion, and calcium intake and absorption. We believe this relationship leads to both a worsening of diabetes and an increased risk of fractures (6), d...

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