Felix Kulozik

Insulin requirements in patients with diabetes and declining kidney function: differences between insulin analogues and human insulin?

Objectives: In diabetic nephropathy the decline of renal function causes modifications of the insulin and carbohydrate metabolism resulting in changed insulin requirements. The aim of the present study was to identify potential differences in the requirements of human insulin and various insulin analogues in patients with type 1 diabetes mellitus and renal dysfunction. Methods: The insulin requirements of 346 patients with type 1 diabetes mellitus under everyday life circumstances were assessed in an observational study. Simultaneously, laboratory parameters were measured and the estimated glomerular filtration rate (eGFR) was calculated using the formula by Cockcroft–Gault. Medical history and concomitant medication were recorded. The insulin requirements of long- and short-acting insulin were tested for a relationship with the eGFR and laboratory parameters. Results: The dosage of long-acting human insulin did not show any relation to eGFR. In contrast, a strong positive relation between dosage and renal function was found for insulin glargine and insulin detemir. After classification according to renal function, the insulin dosage at eGFR less than 60 ml/min was 29.7% lower in glargine-treated and 27.3% lower in detemir-treated patients compared with eGFR greater than 90 ml/min. Considering the whole range of eGFR, short-acting human insulin did not show a relation with renal function. Only after classification according to renal function was a dose reduction found for human insulin at eGFR less than 60 ml/min. In contrast, requirements of insulin lispro were significantly related to eGFR over the whole range of eGFR. At eGFR less than 60 ml/min the insulin dosage was 32.6% lower than at eGFR greater than 90 ml/min. The requirements of insulin aspart did not show any association with the eGFR. Conclusions: Patients with type 1 diabetes mellitus show different insulin requirements according to the renal function depending on the applied insulin. This finding is essential for the adjustment of insulin therapy in patients with diabetic nephropathy to achieve balanced glycemic control. To determine the underlying mechanisms, further studies on the pharmacokinetics and pharmacodynamics of the different insulins in patients with diabetic nephropathy are needed.

Analytical Performance of Glucose Monitoring Systems at Different Blood Glucose Ranges and Analysis of Outliers in a Clinical Setting

Background: We investigated the analytical accuracy of 27 glucose monitoring systems (GMS) in a clinical setting, using the new ISO accuracy limits. In addition to measuring accuracy at blood glucose (BG) levels < 100 mg/dl and > 100 mg/dl, we also analyzed devices performance with respect to these criteria at 5 specific BG level ranges, making it possible to further differentiate between devices with regard to overall performance. Methods: Carbohydrate meals and insulin injections were used to induce an increase or decrease in BG levels in 37 insulin-dependent patients. Capillary blood samples were collected at 10-minute intervals, and BG levels determined simultaneously using GMS and a laboratory-based method. Results obtained via both methods were analyzed according to the new ISO criteria. Results: Only 12 of 27 devices tested met overall requirements of the new ISO accuracy limits. When accuracy was assessed at BG levels < 100 mg/dl and > 100 mg/dl, criteria were met by 14 and 13 devices, respectively. A more detailed analysis involving 5 different BG level ranges revealed that 13 (48.1%) devices met the required criteria at BG levels between 50 and 150 mg/dl, whereas 19 (70.3%) met these criteria at BG levels above 250 mg/dl. The overall frequency of outliers was low. Conclusions: The assessment of analytical accuracy of GMS at a number of BG level ranges made it possible to further differentiate between devices with regard to overall performance, a process that is of particular importance given the user-centered nature of the devices’ intended use.

Safety and accuracy of a new long-term subconjunctival glucose sensor

Background:  A new biosensor has been developed by EyeSense (Großostheim, Germany) that is placed into the conjunctiva of one eye to measure the glucose concentration of the surrounding tissue in a non‐invasive manner. In the present study we investigated the correlation between glucose concentrations measured by the EyeSense implant and those determined by finger prick testing, as well as the tolerability and safety of the implant over a 16‐week period.

Influence of renal function on serum concentration of 1,5‐anhydroglucitol in type 2 diabetic patients in CKD stages I‐III: A comparative study with HbA1c and glycated albumin

1,5‐Anhydroglucitol (1,5‐AG) is a new blood glucose control marker reflecting temporary glucose elevations. However, 1,5‐AG is of limited value in patients with advanced renal insufficiency. The aim of the present study was to assess the correlation between 1,5‐AG levels and renal function in patients with earlier stages of nephropathy compared with another two markers of diabetes control, namely HbA1c and glycated albumin (GA).

Treatment with insulin analogs, especially Glargine and Lispro, associates with better renal function and higher hemoglobin levels in Type 1 diabetic patients with impaired kidney function:

Objectives: The influence of type of insulin treatment - insulin analogs versus human insulin - on the development of diabetes related vascular complications has been sparsely investigated. We examine here possible differences regarding kidney function and hemoglobin levels. Methods: Multiple linear regression was used to investigate the relationship between the following characteristics measured in 509 type 1 diabetic patients who were recruited in an outpatient practice: current clinical status and treatment modalities, type of injected insulin and the routine laboratory parameters hemoglobin, HbA1c, serum creatinine, eGFR, hs CRP and urinary albumin/creatinine ratio. Results: Compared with human insulin, multiple regression analysis taking into account possible confounders revealed that treatment with insulin analogs was associated with increased eGFR (+7.1 ml/min; P=0.0002), lower urinary albumin/creatinine ratio (ratio logarithm -0.4; P=0.003) and higher hemoglobin concentration (+0.31 g/dl; P=0.04). Stratification by type of insulin showed the best renal status for treatment with insulins Glargine and Lispro. Differences were consistent both for patients with normal (eGFR → 90 ml/min) and with an impaired (eGFR ← 90 ml/min) kidney function. Conclusions: Present results suggest that treatment of type 1 diabetic patients with normal and impaired renal function with insulin analogs, especially Glargine and Lispro, is associated with better kidney function, lower urinary albumin/creatinine ratio and lower hemoglobin concentration compared to therapy with human insulin. If confirmed by other studies, treatment with insulin analogs may be a further possibility in delaying progression of nephropathy and in preventing early hemoglobin decline.

Effect of renal function on serum concentration of 1,5-anhydroglucitol in type 2 diabetic patients in chronic kidney disease stages I–III: A comparative study with HbA1c and glycated albumin

1,5‐Anhydroglucitol (1,5‐AG) is a new blood glucose control marker reflecting temporary glucose elevations. However, 1,5‐AG is of limited value in patients with advanced renal insufficiency. The aim of the present study was to assess the correlation between 1,5‐AG levels and renal function in patients with earlier stages of nephropathy compared with another two markers of diabetes control, namely HbA1c and glycated albumin (GA).

Glycated albumin and HbA1c as predictors of mortality and vascular complications in type 2 diabetes patients with normal and moderately impaired renal function: 5-year results from a 380 patient cohort

Abstract Background: Glycated albumin (GA) represents a better marker of glycemic control than HbA1c in patients with renal failure. Studies on the clinical impact of GA in patients with normal or moderately impaired