Krzysztof Strojek

Effects of Prandial Versus Fasting Glycemia on Cardiovascular Outcomes in Type 2 Diabetes: The HEART2D trial

OBJECTIVE—Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) is a multinational, randomized, controlled trial designed to compare the effects of prandial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS—Patients (type 2 diabetes, aged 30–75 years) were randomly assigned within 21 days after AMI to the 1) prandial strategy (PRANDIAL) (three premeal doses of insulin lispro targeting 2-h postprandial blood glucose <7.5 mmol/l) or the 2) basal strategy (BASAL) (NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose <6.7 mmol/l). RESULTS—A total of 1,115 patients were randomly assigned (PRANDIAL n = 557; BASAL n = 558), and the mean patient participation after randomization was 963 days (range 1–1,687 days). The trial was stopped for lack of efficacy. Risks of first combined adjudicated primary cardiovascular events in the PRANDIAL (n = 174, 31.2%) and BASAL (n = 181, 32.4%) groups were similar (hazard ratio 0.98 [95% CI 0.8–1.21]). Mean A1C did not differ between the PRANDIAL and BASAL groups (7.7 ± 0.1 vs. 7.8 ± 0.1%; P = 0.4) during the study. The PRANDIAL group showed a lower daily mean postprandial blood glucose (7.8 vs. 8.6 mmol/l; P < 0.01) and 2-h postprandial blood glucose excursion (0.1 vs. 1.3 mmol/l; P < 0.001) versus the BASAL group. The BASAL group showed lower mean fasting blood glucose (7.0 vs. 8.1 mmol/l; P < 0.001) and similar daily fasting/premeal blood glucose (7.7 vs. 7.3 mmol/l; P = 0.233) versus the PRANDIAL group. CONCLUSIONS—Treating diabetic survivors of AMI with prandial versus basal strategies achieved differences in fasting blood glucose, less-than-expected differences in postprandial blood glucose, similar levels of A1C, and no difference in risk for future cardiovascular event rates.

Impact of low frequency pulsed magnetic fields on pain intensity, quality of life and sleep disturbances in patients with painful diabetic polyneuropathy

AIM The aim of this randomized, placebo-controlled, double-blind study was to assess whether a low frequency magnetic field can influence pain intensity, quality of life and sleep, and glycaemic control in patients with painful diabetic polyneuropathy. METHODS Sixty-one patients were randomized into two groups: the study group comprised 32 patients exposed to a low frequency magnetic field, average pain duration 23 months; the control group included 29 patients who received sham exposure, average pain duration 28 months. Patients were exposed for three weeks, 20 min a day, five days a week. The magnetic field generator was a Viofor JPS device (Med & Life, Komorow, Poland). All subjects filled out the following questionnaires five times (at the beginning and after one, two, three and five weeks): SFMPQ-VAS (pain evaluation), EuroQol EQ-5D and MOS Sleep Scale. HbA(1c) was evaluated at baseline and after five weeks. RESULTS Significant reductions in pain intensity were seen in both the study group (visual analogue scale [VAS] value of 73 mm at baseline versus 33 mm after three weeks) and controls (VAS 69 mm at baseline versus 41 mm after three weeks). The extent of pain reduction did not differ significantly between the groups at any time. Also, both groups had similar improvements in EuroQol, MOS and HbA(1c) values. CONCLUSION Genuine magnetic field exposure has no advantage over sham exposure in reducing pain intensity, improving quality of life, and decreasing sleep disturbances and HbA(1c).

Incidence of Fractures in Patients With Type 2 Diabetes in the SAVOR-TIMI 53 Trial

OBJECTIVE Patients with type 2 diabetes have an increased risk of bone fractures, the predisposing factors for which are unknown. Treatment with thiazolidinediones (TZDs) further increases the incidence of osteoporotic fractures. In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial, fractures were considered an adverse event of special interest, and information regarding fractures was collected. RESEARCH DESIGN AND METHODS We compared the incidence of fractures among the 8,280 patients who were assigned to treatment with saxagliptin with that in the 8,212 patients who were assigned to placebo. We further analyzed the participants’ baseline characteristics and fracture risk. RESULTS During a median follow-up of 2.1 years, 241 patients (2.9%) in the saxagliptin group and 240 (2.9%) in the placebo group experienced a fracture (hazard ratio [HR] 1.00 [95% CI 0.83–1.19]). Event rates for fractures were the same in both treatment arms: 14.7 per 1,000 patient-years in the entire population and 14.0 in the on-treatment population (first event only). Fracture risk was similar in patients treated with saxagliptin or placebo across different subgroups defined by race, cardiovascular risk, and renal function. A multivariable Cox regression analysis showed that risk of fracture was associated with female sex (P < 0.0001), longer diabetes duration (P < 0.0001), older age (P = 0.002), major hypoglycemic events (P = 0.01), noncompliance with study drug (P = 0.01), and treatment with TZDs (P = 0.03). CONCLUSIONS In a large population of older patients with type 2 diabetes, treatment with saxagliptin was not associated with an increased risk of fractures. The association between longer diabetes duration and increased risk of bone fracture is an intriguing finding.

The prognostic value of different glucose abnormalities in patients with acute myocardial infarction treated invasively

BackgroundDiabetes (DM) deteriorates the prognosis in patients with coronary heart disease. However, the prognostic value of different glucose abnormalities (GA) other than DM in subjects with acute myocardial infarction (AMI) treated invasively remains unclear.AimsTo assess the incidence and impact of GA on clinical outcomes in AMI patients treated with percutaneous coronary intervention (PCI).MethodsA single-center, prospective registry encompassed 2733 consecutive AMI subjects treated with PCI. In all in-hospital survivors (n = 2527, 92.5%) without the history of DM diagnosed before or during index hospitalization standard oral glucose tolerance test (OGTT) was performed during stable condition before hospital discharge and interpreted according to WHO criteria. The mean follow-up period was 37.5 months.ResultsThe incidence of GA was as follows: impaired fasting glycaemia - IFG (n = 376, 15%); impaired glucose tolerance - IGT (n = 560, 22%); DM (n = 425, 17%); new onset DM (n = 384, 15%); and normal glucose tolerance – NGT (n = 782, 31%). During the long-term follow-up, death rate events for previously known DM, new onset DM and IGT were significantly more frequent than those for IFG and NGT (12.3; 9.6 and 9.4 vs. 5.6 and 6.4%, respectively, P < 0.05). The strongest and common independent predictors of death in GA patients were glomerular filtration rate < 60 ml/min/1,73 m^2 (HR 2.0 and 2.8) and left ventricle ejection fraction < 35% (HR 2.5 and 1.8, all P < 0.05) respectively.ConclusionsGlucose abnormalities are very common in AMI patients. DM, new onset DM and IGT increase remote mortality. Impaired glucose tolerance bears similar long-term prognosis as diabetes.

Self-monitoring of blood glucose in treatment of type 2 diabetes

Blood glucose measurements are important components of a effective diabetes management. Self-monitoring of blood glucose (SMBG) provides the possibility for collecting information on glucose levels at different timepoints and facilitates patient empowerment. However, the efficacy of SMBG in particular groups of patients is controversial. Self-monitoring is postulated to have a beneficial effect on metabolic control in type 1 diabetes as it is essential to adjust insulin doses. In type 2 diabetes the efficacy of frequent glucose measurements remains uncertain. The purpose of this paper is to overview recent data in the field of self-control to evaluate the influence of SMBG on glycaemic control in type 2 diabetes. The results of studies suggest that SMBG can have an important role in improving metabolic control if it is an integral part of a wider educational strategy. SMBG can be especially recommended for type 2 diabetic patients with suboptimal metabolic control in order to promote dietary and lifestyle changes as well as treatment correction as a response to feedback provided by blood glucose results.

Metformin — a new old drug

For many years metformin has been the gold standard in the treatment of type 2 diabetes. According to recommendations of the most important diabetes associations, this is the first-choice drug for use as monotherapy in patients with newly diagnosed type 2 diabetes. Metformin is also recommended in combined treatment when monotherapy is no longer effective. It is then combined with a sulfony-lurea, an incretin, flozin, or insulin, irrespective of the number of insulin injections per day. Besides its properties used in the treatment of diabetes, metformin has been treated for some time as a drug of a so-called pleiotropic activity, as each year brings new reports about its favourable effect in different conditions. At present, the scope of reimbursed indications of this drug has been expanded to include prediabetes, insulin resistance syndromes, and polycystic ovary syndrome. Metformin does not stimulate insulin secretion by the beta cells of the pancreas, and thus it is a drug that does not cause hypoglycaemia. The blood glucose-lowering effect of the drug is a consequence of hepatic glucose production inhibition, and of peripheral tissue (muscle tissue, fatty tissue) sensitisation to the effect of insulin of both endogenous and exogenous origin. The exact mechanism of metformin action at the cellular level remained unknown for a long time. Studies performed in recent years have provided a great deal of information that enables better understanding of the mechanism of action of the drug as well as the clinical effects resulting from its use. Metformin, besides improvement of glycaemia, is neutral to body weight, is cardioprotective, improves lipid profile, and has a probable anti-cancer effect. Metformin accumulation in the intestinal mucosa may interfere with FDG (18F-deoxyglucose) PET-CT image assessment. The aim of this article is a detailed discussion of metformin properties, its mechanisms of action, and clinical effects.

Is there an impact of treatment with DPP-4 inhibitors on lymphocyte subpopulations in type 2 diabetic patients?

INTRODUCTION Dipeptidil peptidase 4 inhibitors (DPP-4) are a group of antihyperglycemic agents. DPP-4 is an enzyme expressed on lymphocyte surface as co-stimulatory molecule in activation processes. The aim was to assess lymphocyte subpopulations initially and after 14 days of treatment with DPP-4 inhibitors sitagliptin, saxagliptin and vildagliptin. MATERIAL AND METHODS The study was conducted in three groups 10 subjects each, of type 2 diabetic patients. In subjects studied an initial tests followed by repeated ones after 14 days of treatment with sitagliptin, saxagliptin, and vildagliptin in therapeutic doses were performed. Baseline test as well as lymphocyte subpopulations (total T cells, and T-cell subsets CD4+, CD8+, CD26+, CD45RA+, CD45RO+, CD4+/CD25+) using 7-colour flow cytometry method were performed. RESULTS In patients receiving sitagliptin no significant increase in lymphocyte subpopulations were observed. In patients who received vildagliptin significant increase of total T-cells (p < 0.05); in patients treated with saxagliptin significant (p < 0.05) though mild increased percentage of total T-cells and CD4+, CD26+, CD45RO+ subsets were found. CONCLUSIONS The study showed mild but significant increase of several T-cell subsets after treatment with saxagliptin and vildagliptin with non significant elevation after treatment with sitagliptin. It seems that changes are not expressed enough to have a clinical impact.

Impact of low-frequency pulsed magnetic fields on defensin and CRP concentrations in patients with painful diabetic polyneuropathy and in healthy subjects.

Aim. The aim was to assess whether magnetic field influences defensin and CRP concentrations in patients with diabetic polyneuropathy and in healthy subjects. Methods. 61 diabetic patients were randomly divided into 2 groups: study group—32 patients exposed to low-frequency magnetic field; and control group—29 patients with sham exposure. Additionally, 20 healthy subjects exposed to low-frequency magnetic field. Exposures were performed during 3 weeks, 5 days in a week. Defensin and CRP concentrations were measured at baseline, after 3 weeks and at the end of the study. Results. There were no significant changes in defensin concentration in patients with diabetes in both the real and sham exposure group. We observed increased concentration of defensin in healthy subjects in week 5 vs. baseline value (P<0.02). Conclusions. Magnetic field has no impact on defensin concentration in diabetic patients but has positive influence on this parameter in healthy subjects.

Perspectives of Patients with Insulin-Treated Type 1 and Type 2 Diabetes on Hypoglycemia: Results of the HAT Observational Study in Central and Eastern European Countries

IntroductionThe aim of this study was to determine the level of awareness of hypoglycemia, the level of fear for hypoglycemia, and the response to hypoglycemic events among insulin-treated diabetes patients from Central and Eastern Europe (CEE). The impact of hypoglycemia on the use of healthcare resources and patient productivity was also assessed.MethodsThis was a multicenter, non-interventional, two-part, patient self-reported questionnaire study that comprised both a retrospective cross-sectional evaluation and a prospective observational evaluation. Study participants were insulin-treated adult patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) from CEE.ResultsMost patients (85.4% T1DM and 83.6% T2DM) reported normal hypoglycemia awareness. The median hypoglycemia fear score was 5 out of 10 for T1DM and 4 out of 10 for T2DM patients. Patients increased glucose monitoring, consulted a doctor/nurse, and/or reduced the insulin dose in response to hypoglycemia. As a consequence of hypoglycemia, patients took leave from work/studies or arrived late and/or left early. Hospitalization was required for 31 (1.2%) patients with T1DM and 66 (2.1%) patients with T2DM.ConclusionHypoglycemia impacts patients’ personal and social functioning, reduces productivity, and results in additional costs, both direct (related to increased use of healthcare resources) and indirect (related to absenteeism.FundingNovo Nordisk.

Assessment of compliance to self monitoring of blood glucose in type 2 diabetic patients and level of implementation of Polish Diabetes Association Recommendation for general practitioners

Introduction. Self monitoring of blood glucose is one of basic elements of effective diabetes treatment. Due to proper self monitoring of blood glucose adequate modification of diabetes treatment — fulfilling criteria of good glycemic control — is possible. Effective treatment enables prevention of late diabetic complications — a cause of disability or death in diabetic population. Material and methods. 765 type 2 diabetic patients (above 18 yrs) treated with both oral hypoglycaemic drugs or insulin in different schemes were observed (mean age: 64.5 ± 10.9 yrs). Therapy was in line with general standards of treatment, medication choice was based on indications and previous independent physician decision. Patients were given glucometer ContourPlus and were taught how to use it and how often measurement had to be taken (on the basis of Polish Diabetes Association Recommendation for 2016). After 3 months (± 2 weeks) assessment of compliance to self monitoring of blood glucose was performed. Additionally, level of implementation of Polish Diabetes Association Recommendation for general practitioners, functionality of glucometer and usefulness of “second chance” measurement were evaluated. Results. 440 participants completely fulfilled recommendations (65.1%) of general practitioner (investigator) regarding self monitoring documentation (type of documentation provided: glucometer, glucose monitoring diary). In investigators opinion, 315 patients (below 50%) were conscientiously compliant to self monitoring of blood glucose based on Polish Diabetes Association Recommendations. In general practice for about 68.0% of patients (n = 506) Polish Diabetes Association Recommendations for self blood glucose monitoring were implemented. Based on investigators opinion the most important features of glucometers which determine effectiveness of self monitoring of glucose are: simplicity, high capacity memory, accuracy and precision of measurement, evaluation of mean glucose in general and mean pre-/after meal. 67.7% patients (n = 451) regarded possibility of “second chance” measurement in glucometer ContourPlus as useful in daily self monitoring of blood glucose. Conclusions. Discrepancy between Polish Diabetes Association Recommendations of self blood glucose monitoring and its realization by type 2 diabetic patients, carried out by general practitioners, was observed. Effective glucose monitoring is dependent on tight cooperation between doctor and patient.