Efficacy and safety of patient-directed titration of once-daily pre-dinner premixed biphasic insulin aspart 70/30 injection in Japanese type 2 diabetic patients with oral antidiabetic drug failure: STEP-AKITA study.

Unlabelled: Aims/Introduction:  To clarify clinical characteristics related to optimal glycemic control achieved after adding once-daily pre-dinner biphasic insulin aspart 70/30 (BIAsp 30) in Japanese type 2 diabetic (T2D) patients with oral antidiabetic drug (OAD) failure.

Materials And Methods:   Under this regimen, we evaluated changes in HbA1c levels and daily self-monitoring blood glucose (BG) profiles, as well as the incidences of hypoglycemia and retinopathy progression. The patients adjusted BIAsp 30 dosages themselves every 3-4 days according to a pre-determined algorithm to achieve fasting BG levels of 101-120 mg/dL.

Diurnal changes in urinary excretion of IgG, transferrin, and ceruloplasmin depend on diurnal changes in systemic blood pressure in normotensive, normoalbuminuric type 2 diabetic patients.

Previous studies of diabetic patients indicate that increased urinary excretion of certain plasma proteins (molecular radii <55 A), such as IgG, transferrin, and ceruloplasmin, precede the development of microalbuminuria. Moreover, increases in these urinary proteins predict future development of microalbuminuria. To clarify whether blood pressure changes influence urinary excretion of these proteins, we examined relationships between diurnal blood pressure changes measured by ambulatory blood pressure monitoring and urinary excretion of IgG, transferrin, ceruloplasmin, alpha2-macroglobulin (88 A) and albumin (36 A) measured separately during the day and night in 20 healthy controls and 26 normotensive, normoalbuminuric diabetic patients.

Effects of antidiabetic treatment with metformin and insulin on serum and adipose tissue adiponectin levels in db/db mice.

Decreased circulating levels of adiponectin, a novel adipose-derived adipocytokine, in obesity possibly contribute to the development of insulin resistance which is a major factor in the pathogenesis of type 2 diabetes. The present study was conducted to examine whether circulating and adipose tissue adiponectin levels are modulated by chronic treatment with metformin and intensive treatment with insulin in murine models of obesity and type 2 diabetes, db/db mice with a C57BL/KsJ genetic background. Nine-week-old male db/db mice were treated with metformin, insulin, and vehicle for 4 weeks.

Enhanced urinary adiponectin excretion in IgA-nephropathy patients with proteinuria.

Adiponectin is secreted specifically by adipose tissue. It was reported that the serum adiponectin level was markedly increased in patients with end-stage renal disease and was positively associated with abnormal renal function in type 2 diabetes. Recently, we found that urinary adiponectin level was significantly increased in type 2 diabetic patients with overt diabetic nephropathy, but not in those without nephropathy.

Urinary excretion of transferrin and orosomucoid are increased after acute protein loading in healthy subjects.

Background/aims: The aim of this study was to elucidate what kind of plasma proteins would change their urinary excretions when the glomerular filtration rate (GFR) was increased.

Methods: We measured urinary excretions of three plasma proteins with different molecular radii (MR) and isoelectric points (pI): albumin, orosomucoid (OM) and transferrin (Tf), after acute protein loading in healthy subjects.

Results: Urinary excretion of OM with more anioic charge and smaller MR than albumin, and Tf with more cationic charge and slightly larger molecular weight than albumin, significantly increased in parallel with increased creatinine clearances after acute protein loading.

Parallel increase in urinary excretion rates of immunoglobulin G, ceruloplasmin, transferrin, and orosomucoid in normoalbuminuric type 2 diabetic patients.

Objective: Increased urinary excretions of several plasma proteins with different molecular radii <55 A and different isoelectric points (pI), such as IgG, ceruloplasmin, transferrin, and orosomucoid, have been independently reported to precede the development of microalbuminuria in diabetic patients. We examined whether increases in urinary excretions of these proteins would be in parallel in the same patient.

Research Design And Methods: Urinary excretion rates of proteins mentioned above in timed overnight urine samples were evaluated in 61 normoalbuminuric type 2 diabetic patients (group D) aged 40-60 years and in 17 age-matched control subjects (group C).

Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy.

Adiponectin, a novel adipose-derived adipocytokine, has beneficial effects not only on improvement of insulin sensitivity but also on mitigation of vascular damage. To evaluate whether adiponectin is implicated in the pathogenesis of diabetic nephropathy characterized by microvascular damage, we examined urinary and serum adiponectin levels in type 2 diabetic patients with different stages of nephropathy. We first confirmed adiponectin is excreted into urine through Western blot analysis, followed by measurements of urinary and serum adiponectin levels by radioimmunoassay.

Increased urinary excretion of monocyte chemoattractant protein-1 in proteinuric renal diseases.

Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is produced mainly by tubular epithelial cells in kidney and contributes to renal interstitial inflammation and fibrosis. More recently, we have demonstrated that urinary MCP-1 excretion is increased in proportion to the degree of albuminuria (proteinuria) and positively correlated with urinary N-acetylglucosaminidase (NAG) levels in type 2 diabetic patients. Based on these findings, we have suggested that heavy proteinuria, itself, probably aggravates renal tubular damage and accelerates the disease progression in diabetic nephropathy by increasing the MCP-1 expression in renal tubuli.

Association of monocyte chemoattractant protein-1 with renal tubular damage in diabetic nephropathy.

Monocyte chemoattractant protein-1 (MCP-1), is a chemokine that mediates renal interstitial inflammation, tubular atrophy, and interstitial fibrosis by recruiting monocytes/macrophages into renal tubulointerstitium. Recent studies have demonstrated that protein overload in renal tubular cells up-regulates MCP-1 gene and its protein expression. Therefore, we hypothesized that increased expression of MCP-1 in renal tubuli, probably triggered by an increase in the leakage of plasma protein from glomerular capillary to tubular fluid, may contribute to renal tubular damage and accelerate the progression of diabetic nephropathy.

Increased urinary excretion of N-acetylglucosaminidase in subjects with impaired glucose tolerance.

N-acetylglucosaminidase (NAG) is a lysosomal enzyme produced by renal proximal tubular cells and has been widely used as a marker, which indicates a degree of renal tubular damage. An increase in urinary NAG excretion is though to result from the renal tubular damage. The aim of this study was to evaluate whether even mild hyperglycemia causes an increase in urinary excretion of NAG, which is a renal tubular protein.

Effects of chronic intake of vegetable protein added to animal or fish protein on renal hemodynamics.

Background/aims: To examine whether chronic intake of vegetable protein added to animal protein diet affects renal hemodynamics or not, we studied effects of three kinds of diets containing various amounts of animal and vegetable protein with 1-week dietary program in each on renal hemodynamics.

Methods: The crossover design of different amounts of vegetable protein added to the constant amount of animal protein was applied to two groups of 7 healthy individuals after the control dietary program. Renal function and 24 hours' urinary albumin excretion rate (AER) were examined on every 7th day of three consecutive 1-week dietary programs.

Glycemic control reverses increases in urinary excretions of immunoglobulin G and ceruloplasmin in type 2 diabetic patients with normoalbuminuria.

To examine whether urinary excretions of plasma proteins with molecular radii of 45-55 A and different isoelectric points such as IgG (pI = 7.4) and ceruloplasmin (pI = 4.4) increase selectively in normoalbuminuric type 2 diabetic patients, urinary albumin excretion rate (AER), renal clearances of IgG, ceruloplasmin and alpha2-macroglobulin, and creatinine clearance (Ccr) were studied in timed overnight urine samples of 36 diabetic outpatients and 16 control subjects.

No association of glutathione S-transferase M1 gene polymorphism with diabetic nephropathy in Japanese type 2 diabetic patients.

Oxidative stress possibly contributes to the development of diabetic nephropathy. Therefore, the levels of endogenous antioxidants may be one of determinants of the susceptibility to diabetic nephropathy. Glutathione S-transferases (GSTs) can work as one of endogenous antioxidants to protect cells from oxidative stress.