Comparison of Glomerular Filtration Rate Estimation from Serum Creatinine and Cystatin C in HNF1A-MODY and Other Types of Diabetes.

INTRODUCTION: We previously showed that in HNF1A-MODY the cystatin C-based glomerular filtration rate (GFR) estimate is higher than the creatinine-based estimate. Currently, we aimed to replicate this finding and verify its clinical significance. METHODS: The study included 72 patients with HNF1A-MODY, 72 with GCK-MODY, 53 with type 1 diabetes (T1DM), 70 with type 2 diabetes (T2DM), and 65 controls. Serum creatinine and cystatin C levels were measured. GFR was calculated from creatinine and cystatin C using the CKD-EPI creatinine equation (eGRF-cr) and CKD-EPI cystatin C equation (eGFR-cys), respectively. RESULTS: Cystatin C levels were lower (p < 0.001) in the control (0.70 ± 0.13 mg/L), HNF1A (0.75 ± 0.21), and GCK (0.72 ± 0.16 mg/L) groups in comparison to those with either T1DM (0.87 ± 0.15 mg/L) or T2DM (0.9 ± 0.23 mg/L). Moreover, eGFR-cys was higher than eGRF-cr in HNF1A-MODY, GCK-MODY, and the controls (p = 0.004; p = 0.003; p < 0.0001). This corresponded to 8.9 mL/min/1.73 m2, 9.7 mL/min/1.73 m2, and 16.9 mL/min/1.73 m2 of difference. Additionally, T1DM patients had higher eGFR-cr than eGFR-cys (11.6 mL/min/1.73 m(2); p = 0.0004); no difference occurred in T2DM (p = 0.91). CONCLUSIONS: We confirmed that eGFR-cys values in HNF1A-MODY patients are higher compared to eGFR-cr. Some other differences were also described in diabetic groups. However, none of them appears to be clinically relevant.

Number of circulating pro-angiogenic cells, growth factor and anti-oxidative gene profiles might be altered in type 2 diabetes with and without diabetic foot syndrome.

AIMS/INTRODUCTION: Type 2 diabetes is often complicated by diabetic foot syndrome (DFS). We analyzed the circulating stem cells, growth factor and anti-oxidant gene expression profiles in type 2 diabetes patients without or with different forms of DFS. MATERIALS AND METHODS: Healthy volunteers (n = 13) and type 2 diabetes patients: (i) without DFS (n = 10); or with (ii) Charcot osteoneuropathy (n = 10); (iii) non-infected (n = 17); (iv) infected (n = 11); and (v) healed ulceration were examined (n = 12). Peripheral blood endothelial progenitor cells (EPC), mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and very small embryonic-like (VSEL) cells were phenotyped using flow cytometry. Plasma cytokine concentrations and gene expressions in blood cells were measured by Luminex and quantitative real-time polymerase chain reaction assays, respectively. RESULTS: Patients with non-complicated type 2 diabetes showed reduced HMOX1 expression, accompanied by HMOX2 upregulation, and had less circulating EPC, MSC or HSC than healthy subjects. In contrast, VSEL cells were elevated in the type 2 diabetes group. However, subjects with DFS, even with healed ulceration, had fewer VSEL cells, more CD45-CD29(+)CD90(+)MSC, and upregulated HMOX1 when compared with the type 2 diabetes group. Patients with Charcot osteopathy had lowered plasma fibroblast growth factor-2. Elevated plasma tumor necrosis factor-α and decreased catalase expression was found in all diabetic patients. CONCLUSIONS: Patients with type 2 diabetes and different forms of DFS have an altered number of circulating stem cells. Type 2 diabetes might also be associated with a changed plasma growth factor and anti-oxidant gene expression profile. Altogether, these factors could contribute to the pathogenesis of different forms of DFS.

Intensifying existing premix therapy (BIAsp 30) with BIAsp 50 and BIAsp 70: A consensus statement.

In 2009, consensus guidelines were published on intensification of insulin therapy using the premix analog biphasic insulin aspart (BIAsp) 30 in the treatment of type 2 diabetes, based on the recommendations of an international, independent expert panel. The guidelines included recommendations and titration algorithms for intensification from basal insulin once (OD) or twice daily (BID) to BIAsp 30 BID, from OD BIAsp 30 to BID, and from BID BIAsp 30 to three times daily (TID). Building on these recommendations, the objective was to develop similar, simple and effective guidelines for intensification switch from a BIAsp 30 to a mid-/high-ratio premix regimen for the vast majority of patients with type 2 diabetes. A panel of independent experts with extensive clinical experience in premix analog therapy met in October 2009 to review the therapeutic role of mid- and high-ratio premixes (BIAsp 50 and 70, respectively). The panel outlined a series of algorithms for intensifying BIAsp 30 BID and TID with mid-/high-ratio premixes, along with practical suggestions relating to intensification for individual patients. A simple tool to aid dose adjustment was also developed. The guidelines suggested here should assist physicians in introducing mid-/high-ratio premixes to optimize the insulin therapy of patients with type 2 diabetes who are failing to achieve glycemic targets on a BIAsp 30 BID or TID regimen.