Insulin pump therapy started at the time of diagnosis: effects on glycemic control and pancreatic β-cell function in type 1 diabetes.

Background: In the interest of preserving residual insulin secretory capacity present at the time of diagnosis with type 1 diabetes (T1D), we compared the efficacy of starting insulin pump therapy at diagnosis with standard multiple daily insulin injections (MDIs).

Methods: We conducted a prospective, randomized, pilot trial comparing MDI therapy with continuous subcutaneous insulin therapy (pump therapy) in 24 patients, 8-18 years old, with newly diagnosed T1D. Subjects were evaluated at enrollment and 1, 3, 6, 9, and 12 months after initial diagnosis of T1D.

Disease and gender-specific dysregulation of NGAL and MMP-9 in type 1 diabetes mellitus.

Neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of renal injury, can bind matrix metalloproteinase-9 (MMP-9) and inhibit its degradation, thereby sustaining MMP-9 proteolytic activity. MMP-9 is produced by renal podocytes, and podocyte MMP production can be modified by high ambient glucose levels. Moreover, dysregulation of MMP-9 activity, gene expression, or urine concentrations has been demonstrated in T2DM-associated nephropathy and in non-diabetic proteinuric renal diseases.

Enhanced excretion of vitamin D binding protein in type 1 diabetes: a role in vitamin D deficiency?

Context: Vitamin D deficiency is an increasingly recognized comorbidity in patients with both type 1 (T1D) and type 2 diabetes, particularly associated with the presence of diabetic nephropathy.

Objective: Because we have previously reported enhanced excretion of megalin in the urine of T1D patients with microalbuminuria, we hypothesized that concurrent urinary loss of the megalin ligand, vitamin D binding protein, might contribute mechanistically to vitamin D deficiency.

Design And Participants: Examining a study cohort of 115 subjects with T1D, aged 14-40 yr, along with 55 age-matched healthy control subjects, we measured plasma and urine concentrations of vitamin D binding protein (VDBP) along with serum concentrations of total calcium, parathyroid hormone, 25-hydroxyvitamin D, and 1, 25-dihydroxyvitamin D; these results were compared between groups and investigated for relationships with metabolic control status or with albuminuria.

Microalbuminuria in type 1 diabetes is associated with enhanced excretion of the endocytic multiligand receptors megalin and cubilin.

Objective: Proteinuria is the hallmark of diabetic nephropathy; yet, glomerular histology does not fully explain mechanisms contributing to proteinuria. Our objective was to identify proteins in the urine of individuals with type 1 diabetes and microalbuminuria that might implicate a mechanistic pathway operative in proteinuria.

Research Design And Methods: Using a GeLC/MS platform proteomics approach, we compared the urine proteome from 12 healthy nondiabetic individuals, 12 subjects with type 1 diabetes yet normal urinary albumin excretion rates, and 12 subjects with type 1 diabetes and microalbuminuria (type 1 diabetes + microalbuminuria).

Matrix metalloproteinase-2 dysregulation in type 1 diabetes.

Objective: Dysregulation of matrix metalloproteinase (MMP)-2 may contribute pathologically to the development of diabetes complications, including diabetic retinopathy and coronary and peripheral arterial disease. Our objective was to explore whether systemic MMP-2 dysregulation could be demonstrated in type 1 diabetes and to determine how MMP-2 concentration relates to disease status.

Research Design And Methods: In this cross-sectional study, MMP-2 concentrations and MMP-2 activity were measured in plasma and timed urine samples from 93 type 1 diabetic and 50 healthy control subjects, aged 14-40 years.