Insulin in Type 1 and Type 2 Diabetes-Should the Dose of Insulin Before a Meal be Based on Glycemia or Meal Content?

The aim of this review was to investigate existing guidelines and scientific evidence on determining insulin dosage in people with type 1 and type 2 diabetes, and in particular to check whether the prandial insulin dose should be calculated based on glycemia or the meal composition, including the carbohydrates, protein and fat content in a meal. By exploring the effect of the meal composition on postprandial glycemia we demonstrated that several factors may influence the increase in glycemia after the meal, which creates significant practical difficulties in determining the appropriate prandial insulin dose. Then we reviewed effects of the existing insulin therapy regimens on glycemic control. We demonstrated that in most existing algorithms aimed at calculating prandial insulin doses in type 1 diabetes only carbohydrates are counted, whereas in type 2 diabetes the meal content is often not taken into consideration. We conclude that prandial insulin doses in treatment of people with diabetes should take into account the pre-meal glycemia as well as the size and composition of meals. However, there are still open questions regarding the optimal way to adjust a prandial insulin dose to a meal and the possible benefits for people with type 1 and type 2 diabetes if particular parameters of the meal are taken into account while calculating the prandial insulin dose. The answers to these questions may vary depending on the type of diabetes.

Accuracy of Automatic Carbohydrate, Protein, Fat and Calorie Counting Based on Voice Descriptions of Meals in People with Type 1 Diabetes.

The aim of this work was to assess the accuracy of automatic macronutrient and calorie counting based on voice descriptions of meals provided by people with unstable type 1 diabetes using the developed expert system (VoiceDiab) in comparison with reference counting made by a dietitian, and to evaluate the impact of insulin doses recommended by a physician on glycemic control in the study’s participants. We also compared insulin doses calculated using the algorithm implemented in the VoiceDiab system. Meal descriptions were provided by 30 hospitalized patients (mean hemoglobin A1c of 8.4%, i.e., 68 mmol/mol). In 16 subjects, the physician determined insulin boluses based on the data provided by the system, and in 14 subjects, by data provided by the dietitian. On one hand, differences introduced by patients who subjectively described their meals compared to those introduced by the system that used the average characteristics of food products, although statistically significant, were low enough not to have a significant impact on insulin doses automatically calculated by the system. On the other hand, the glycemic control of patients was comparable regardless of whether the physician was using the system-estimated or the reference content of meals to determine insulin doses.

Selected RANKL/RANK/OPG system genetic variants in diabetic foot patients.

PURPOSE: Diabetic foot is a complication of long-lasting diabetes mellitus affecting up to 15% of patients, both in type 1 and type 2 diabetes. Osteoprotegerin is involved in osteogenesis and calcification. The aim of the study was to assess the role of selected osteoprotegerin gene variants in diabetes patients with diabetic foot. METHODS: The study involved 300 patients with diabetes and diabetic foot and 968 healthy controls. The study group was formed by 243 patients with diabetic foot of neuropathic origin, 102 with diabetic foot of neuroischemic origin and 77 with Charcot neuroarthropathy. RESULTS: Compared to controls, rs1872426 and rs1485286 showed correlation with diabetic foot in diabetes subjects. Significant associations between rs2073618, rs1872426, rs7464496 and rs1485286 in men were reported. The aforementioned correlations were also present in type 2 diabetes patient subgroup. Variant rs1485286 was associated to diabetic foot of neuropathic origin. Sex-specificity for females was present for rs6993813 in patients with diabetic foot of neuropathic origin and type 1 diabetes. Variants rs1872426, rs2073617 and rs1485286 were correlated with CN. We found that age, body weight, body mass index, waist circumference, hip circumference and waist-hip ratio were among the basic risk factors of diabetic foot. CONCLUSIONS: The following variants TNFRSF11B (rs2073618, rs2073617, rs1872426, rs1032128, rs7464496, rs11573829 and rs1485286), COLEC10 (rs6993813, rs3134069) and TNFSF11 (rs9533156) present differences in allele frequencies in diabetic foot patients and show correlation with gender, diabetes type and diabetic foot etiology.

Validation of a hemoglobin A1c model in patients with type 1 and type 2 diabetes and its use to go beyond the averaged relationship of hemoglobin A1c and mean glucose level.

BACKGROUND: Glycated hemoglobin A1c (HbA1c) has been used as an index of glycemic control in the management, guidance, and clinical trials of diabetic patients for the past 35 years. The aim of this study was to validate the HbA1c model in patients with type 1 and type 2 diabetes and to use it to support interpretation of HbA1c in different clinical situations. METHODS: The HbA1c model was identified in 30 patients (15 with type 1 diabetes and 15 with type 2 diabetes) by estimating the overall glycation rate constant (k), based on results of continuous glucose monitoring. The model was validated by assessing its ability to predict HbA1c changes in cultures of erythrocytes in vitro and to reproduce results of the A1C-Derived Average Glucose (ADAG) study. The model was used to simulate the influence of different glucose profiles on HbA1c. RESULTS: The mean k was equal to 1.296 ± 0.216 × 10(-9) l mmol(-1) s(-1) with no difference between type 1 and type 2 diabetes. The mean coefficient of variation of k was equal to 16.7%. The model predicted HbA1c levels in vitro with a mean absolute difference less than 0.3% (3.3 mmol/mol). It reproduced the linear relationship of HbA1c and mean glucose levels established in the ADAG study. The simulation experiments demonstrated that during periods of unstable glycemic control, glycemic profiles with the same mean glucose might result in much different HbA1c levels. CONCLUSIONS: Patients with type 1 and type 2 diabetes are characterized by the same mean value of k, but there is considerable interindividual variation in the relationship of HbA1c and mean glucose level. Results suggest that reciprocal changes in glycation rate and the life span of erythrocytes exist in a wide range of HbA1c values. Thus, for an average patient with diabetes, no modifications of parameters of the glycation model are required to obtain meaningful HbA1c predictions. Interpreting HbA1c as a measure of the mean glucose is fully justified only in the case of stable glycemia. The model and more frequent tests of HbA1c might be used to decrease ambiguity of interpreting HbA1c in terms of glycemic control.

Microdialysis monitoring of glucose, lactate, glycerol, and pyruvate in patients with diabetic ketoacidosis.

PURPOSE: The objective was to assess glucose, lactate, glycerol, and pyruvate concentrations in the interstitial fluid of the adipose tissue as well as the glucose relative recovery coefficient in reference to capillary blood (RC) during the first two days of the standard treatment of diabetic ketoacidosis (DKA) in patients with type 1 and type 2 diabetes. MATERIALS AND METHODS: The study group consisted of 19 patients (12 with type 1 diabetes and 7 with type 2 diabetes). The metabolic state of the patients was monitored using the microdialysis technique. The analysis of variance was used to investigate whether the type of diabetes and the duration of treatment influenced the assessed parameters. RESULTS: Concentrations of all the monitored components were stable after the initial 12 h of treatment. Glucose concentration was higher and concentrations of all the other components were lower (p<0.0001) in patients with type 1 diabetes than in patients with type 2 diabetes. Significantly higher RC was observed in patients with type 1 diabetes during the initial 12 h. CONCLUSIONS: The results suggest that the standard treatment of DKA is effective in stabilizing a concentration of the studied metabolic components in the interstitial fluid in patients with type 1 and type 2 diabetes despite differences in the glucose concentration at the beginning of the treatment.

Lactic acidosis in patients with diabetes.

INTRODUCTION: Lactic acidosis is a relatively rare complication diagnosed in patients with diabetes. OBJECTIVES: The aim of this study was to identify causes of lactic acidosis in patients with diabetes and to measure the extent of metabolic disturbances based on the available laboratory test results. PATIENTS AND METHODS: A total of 29 diabetic patients aged 20-87 years were admitted to the Intensive Diabetes Care Unit of the Warsaw Medical University in the years 2007-2012 with the diagnosis of lactic acidosis (lactate level >5 mmol/l). A detailed medical history was taken from all patients or their caregivers. Lactate levels, glycemia, acetonuria, and gasometry were measured on admission. RESULTS: Eight patients with type 1 diabetes, 18 patients with type 2 diabetes, and 3 patients with other types of diabetes were hospitalized with the diagnosis of lactic acidosis. Lactic acidosis (lactate levels, 5.2-27 mmol/l) was associated with increased glycemia (13.3-91.7 mmol/l) and low pH (6.73-7.28). Alcohol abuse was reported in 12 subjects based on medical history. In 3 women, acute diabetic complication was caused by psychogenic eating disorders. There were 5 fatal cases including 3 cases of metformin treatment. CONCLUSIONS: Alcohol abuse and its effects on health seem to be the main cause of lactic acidosis in diabetic patients. Metformin-treated patients, especially elderly ones, are at a risk of sudden deterioration of renal function, which in turn may increase the risk of lactic acidosis.

Hemoglobin glycation rate constant in non-diabetic Individuals.

The objectives were as follows: (1) estimating mean value of the overall hemoglobin glycation rate constant (k); (2) analyzing inter-individual variability of k; (3) verifying ability of the hemoglobin A1c (HbA1c) formation model to predict changes of HbA1c during red blood cells cultivation in vitro and to reproduce the clinical data. The mean k estimated in a group of 10 non-diabetic subjects was equal to 1.257 ± 0.114 × 10(-9) L mmol(-1) s(-1). The mean k was not affected by a way of estimation of glycemia. The mean k differed less than 20% from values reported earlier and it was almost identical to the mean values calculated on basis of the selected published data. Analysis of variability of k suggests that inter-individual heterogeneity of HbA1c formation is limited or rare. The HbA1c mathematical model was able to predict changes of HbA1c in vitro resulting from different glucose levels and to reproduce a linear relationship of HbA1c and average glucose obtained in the A1C-Derived Average Glucose Study. This study demonstrates that the glycation model with the same k value might be used in majority of individuals as a tool supporting interpretation of HbA1c in different clinical situations.

Area of the diabetic ulcers estimated applying a foot scanner-based home telecare system and three reference methods.

BACKGROUND: Diabetic foot ulcer area is a basic parameter used for monitoring the wound healing and effectiveness of the treatment applied. TeleDiaFoS (developed earlier in collaboration with the Department and Clinic of Gastroenterology and Metabolic Diseases, Medical University of Warsaw, Warsaw, Poland) is one of just a few systems available that make possible monitoring of the wound size remotely based on the foot scans transmitted to the physician from a patient's home. The aim of this study was to compare the diabetic foot ulcer areas measured using TeleDiaFoS with the results obtained using three reference methods. METHODS: The reference measurements were conducted using the elliptical method with a ruler, the wound tracing method and planimetrics with the Visitrak (Smith & Nephew, London, UK) system, and the pattern-coded structured light method with the Silhouette (ARANZ Medical, Christchurch, New Zealand) system. Regression and Bland-Altman analyses were performed. The study group consisted of 23 diabetes patients with plantar foot ulcers. RESULTS: Thirty-three wounds were successfully examined. The measurement method influenced the measured area significantly (P=0.00005). The correlation coefficients between TeleDiaFoS and the ruler, Visitrak, and Silhouette methods were 0.949, 0.985, and 0.987, and the limits of agreement equaled -1.3±5.5 cm(2), -0.4±2.2 cm(2), and -0.6±2.1 cm(2), respectively. The strong linear relationships obtained can be used to convert the wound area measured with TeleDiaFoS to the corresponding value of each of the reference methods. CONCLUSIONS: The results indicate that the wound area of plantar ulcers in diabetes might be monitored effectively using the TeleDiaFoS system based on the foot scans that the patient can produce at home with no assistance of other persons.

Monitoring of diabetic foot syndrome treatment: some new perspectives.

Diabetic foot syndrome (DFS) is one of the major complications of diabetes, and it can lead to foot amputations. It is very important to assure good medical care for diabetic patients not only during their stay at hospital but also at home. Telecare can be one good solution for extending medical care to patients' homes. There are some reports regarding the application of new technologies in this field. The standard current model of telecare of DFS includes experts at hospital who conduct clinical examinations and decision making at a distance, in close cooperation with a visiting nurse and the patient. In the present paper a new paradigm of the DFS's telecare is introduced, which eliminates the visiting nurse. The designed and developed TeleDiaFoS system consists of a traditional database and mobile patient's module (PM) allowing for documentation of the foot images as well as the results of blood glucose and blood pressure measurements taken by the patient himself at home. A 2-year validation of the TeleDiaFoS system on 10 DFS patients (3 months each) proved its usefulness and led to acceptance of this type of technical support by patients and physicians. The designed and developed system and proposed sterilization procedure of the PM have been found to be easy to use by the patient at home.

Multicenter, open-label, nonrandomized, observational safety study in subjects using insulin aspart in basal-bolus regimen for the treatment of diabetes.

INTRODUCTION: Basal-bolus insulin therapy is a standard method of intensifying diabetes treatment. A common adverse effect of such treatment is hypoglycemia. Data on frequency of hypoglycemia when fast-acting insulin analogue is used in everyday clinical practice is scarce. OBJECTIVES: The aim of the study was to investigate the risk of hypoglycemia after the use of insulin aspart in basal-bolus therapy in patients with type 1 and 2 diabetes. PATIENTS AND METHODS: It was a multicenter, open-label, noninterventional study. It involved 950 patients with type 1 and 1332 patients with type 2 diabetes who started preprandial insulin aspart in basal-bolus regimen. Patients were followed for 13 weeks. The primary endpoint was the incidence of major daytime and nocturnal hypoglycemic events assessed on the basis of patients' self-reports during follow-up compared with a 4-week period before the baseline visit. Secondary endpoints were: incidence of minor daytime and nocturnal hypoglycemia, hemoglobin A1c (HbA1c), fasting and postprandial glycemia. RESULTS: The rate of major hypoglycemia decreased in patients with type 1 diabetes--the incidence rate ratio (IRR) was 0.14 for daytime and 0.03 for nocturnal episodes (P <0.0001) and did not change in patients with type 2 diabetes. The rate of minor episodes decreased in patients with type 1 diabetes (IRR = 0.44 for daytime and IRR = 0.24 for nocturnal episodes, P <0.0001) and in patients with type 2 diabetes (IRR= 0.57, P <0.0001 for daytime and IRR = 0.89, P <0.05 for nocturnal episodes). HbA1c decreased by 1.28 ± 1.64% in type 1 and 1.25 ± 1.10% in type 2 diabetes (both P <0.0001). Self-measured fasting and postprandial blood glucose levels were significantly lower at the final visit compared with baseline, irrespective of diabetes type. CONCLUSIONS: In clinical practice, treatment with insulin aspart in basal-bolus regimen is associated with low risk of hypoglycemia and leads to a significant improvement in glucose control, irrespective of diabetes type.

Validation of hemoglobin glycation models using glycemia monitoring in vivo and culturing of erythrocytes in vitro.

Glycated hemoglobin A1c (HbA1c) concentration in blood is an index of the glycemic control widely used in diabetology. The aim of the work was to validate two mathematical models of HbA1c formation (assuming irreversible or reversible glycation, respectively) and select a model, which was able to predict changes of HbA1c concentration in response to varying glycemia courses with higher accuracy. The experimental procedure applied consisted of an original combination of: in vivo continuous glucose concentration monitoring, long-term in vitro culturing of the human erythrocytes and mathematical modeling of HbA1c formation in vivo and in vitro with HbA1c values scaled according to the most specific analytical methods. Sixteen experiments were conducted in vitro using blood samples collected from healthy volunteer and stable type 1 diabetic patients whose glycemia was estimated beforehand based on long-term monitoring. The mean absolute difference of the measured and predicted HbA1c concentrations for the in vitro experiments were equal to 0.64 +/- 0.29% and 1.42 +/- 0.16% (p = 0.0007) for irreversible and for reversible model, respectively, meaning that the irreversible model was able to predict the glycation kinetics with a higher accuracy. This model was also more sensitive to a deviation of the erythrocytes life span.

Microdialysis technique as a monitoring system for acute complications of diabetes.

The objective of the study was to establish the quasi-continuous courses, using microdialysis technique, of glucose, lactate, and glycerol concentrations in interstitial fluid of abdominal adipose tissue during the standard treatment of acute diabetes complications. Clinical studies were carried out on 31 diabetic patients during the initial 48 h of the treatment. In all but two obese female patients with hyperglycemic hyperosmolar state (HHS) did glucose concentration in perfusion fluid (PF) reflect concentration in capillary blood. The recovery of glucose correlated with patients' body mass index (r = 0.55). It was significantly higher in lean and overweight patients (91 +/- 15%) than in obese patients (55 +/- 31%). The course of lactate concentration in PF coincided with the course in venous blood (2.1 +/- 0.3 mmol/L vs. 2.0 +/- 0.5 mmol/L, P = 0.35). Glycerol concentration was 267 +/- 41 micromol/L and 133 +/- 40 micromol/L in PF and venous blood, respectively (P = 0.004). The study indicated that microdialysis may be an effective tool to monitor concentration of different metabolites in interstitial fluid of the adipose tissue during treatment of the acute complications of diabetes. Applicability of the technique in the monitoring of HHS, especially in obese female patients, needs further investigation.

[Postprandial glycemia--review of current pathophysiological, epidemiological and clinical aspects]. / Glikemia poposilkowa--przeglad zagadnien patofizjologicznych, epidemiologicznych i klinicznych.

One of the most difficult current medical problems is the growing epidemics of diabetes mellitus. The contemporary treatment aims not only to secure the patients survival and to protect from the acute symptoms but also to avoid the occurrence of the chronic complications of the disease. This paper contains a review of the role that postprandial hyperglycemia plays in the treatment of diabetes mellitus especially type 2. Authors summarize findings of pathophysiological and epidemiological macroangiopathy studies that indicate the use of prandial glucose regulation in clinical practice. This review contains discussion of postulated mechanism in which short-lasting increases in plasma glucose concentration can damage vessel wall lead to atherosclerosis. Epidemiological studies showing the strong correlation between postprandial (and post-challenge) plasma glucose levels with cardiovascular endpoints are also discussed. Moreover, in this paper the reader may find a discussion on practical aspects of postprandial hyperglycemia monitoring in the treatment of diabetic patient, focusing at the relationship between prandial glycaemia and long term glycaemia control expressed by HbA(1c) measurements. The guidelines for monitoring postprandial glycaemia are also included. The modern therapeutic possibilities aiming post-prandial hyperglycaemia are also showed.