Elektra Szymańska-Garbacz

Intensified glucose lowering in type 2 diabetes: time for a bolder reappraisal

To the Editor: We read with great interest the review by Yudkin et al. [1]. The authors, having carefully analysed the available data, concluded that glucose control, while being the weakest amongst the main cardiovascular risk contributors (hypertension + hyperlipidaemia + hyperglycaemia + smoking), is being paid too much attention in the CVD prevention and treatment guidelines. They explain that if it is at all effective, it may prolong life in many patients at best for a matter of days and, furthermore, this would cost a small fortune. Moreover, in the conclusions of the article the authors suggest that intensive glucose management should be used in those individuals with higher (which we understand to mean well over 8.0%) levels of HbA1c, particularly in those of advanced age and diminished life expectancy, and that the target of 6.5–7.0% should be completely abandoned. While we share the general view of the authors and praise their rigid analysis supported by pharmacoeconomic data, looking at data from recent large trials we have arrived at a different conclusion regarding target HbA1c values and the current role of intensified glucose control. In short, the results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and Veterans Affairs Diabetes Trial (VADT) clearly show that aiming to reach a target HbA1c level of <6.5% or <7% is beneficial for those patients with diabetes who are younger and do not have a history of microand macrovascular complications [2, 3]. The ACCORD study was initially interpreted as a warning sign against lowering HbA1c to about 6.5% [2], but the recently published analysis [4] shows that the increase in the mortality rate was largely seen only in those who failed to achieve the target levels of 6.5%. Furthermore, the HbA1c level above which the risk of death rose substantially among those in the intensive treatment arm was about 7.0%, indicating that those who reached the intensive treatment target died less often than those who did not [4]. W. C. Duckworth, co-principal investigator of the VADT, announced at the American Diabetes Association meeting in June 2009: ‘We found that initiation of intensive control in the first 15 years after a diagnosis of type 2 diabetes reduced the risk of cardiovascular events, including mortality, but initiation 16–20 years after diagnosis yielded no such benefit. Further, initiation of intensive control 20 or more years after diagnosis increased the risk of cardiovascular events in the population studied in this trial’ [5]. A meta-analysis of the ACCORD study, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study, UK Prospective Diabetes Study (UKPDS) and VADT, performed by the Collaborators on Trials of Lowering Glucose (CONTROL) group, confirmed that achievement of an HbA1c level of <6.5% provides benefits L. Czupryniak (*) : E. Szymanska-Garbacz :M. Pawlowski : M. Saryusz-Wolska : J. Loba Internal Medicine and Diabetology Department, Barlicki University Hospital No. 1, Medical University of Lodz, Lodz, Poland e-mail: czupryniak@yahoo.co.uk

Differences in risk factors of malignancy between men and women with type 2 diabetes: A retrospective case-control study

Background The aim of this multicenter, retrospective, case-control study was to identify differences in risk factors of malignancy between men and women with type 2 diabetes. Results Among women the most prevalent malignancies were: breast and uterine cancers (35.6% and 14.4% respectively), while among men there were: colorectal and prostate cancers (24.5% and 13.3% respectively). In both gender metformin use was associated with lower cancer risk. Obesity and insulin treatment in dose-dependent and time-varying manner were associated with significantly increased risk of malignancy in females. In men, unexpectedly, cardiovascular disease was more prevalent in control group. Other variables did not show significant association with malignancy risk. Materials and Methods 118 women and 98 men with type 2 diabetes mellitus who developed cancer after diagnosis of diabetes and the same number of strictly age matched controls with type 2 diabetes and without malignancy were included into the study. Diabetes duration, antidiabetic medications use, glycated hemoglobin level, body mass index, smoking habits, occupation, presence of comorbidities and aspirin use were included into analyses. Conclusions Metformin demonstrated protective effect against cancer in both sexes. Obesity and insulin treatment seem to have greater impact on cancer risk among women.BACKGROUND The aim of this multicenter, retrospective, case-control study was to identify differences in risk factors of malignancy between men and women with type 2 diabetes. RESULTS Among women the most prevalent malignancies were: breast and uterine cancers (35.6% and 14.4% respectively), while among men there were: colorectal and prostate cancers (24.5% and 13.3% respectively). In both gender metformin use was associated with lower cancer risk. Obesity and insulin treatment in dose-dependent and time-varying manner were associated with significantly increased risk of malignancy in females. In men, unexpectedly, cardiovascular disease was more prevalent in control group. Other variables did not show significant association with malignancy risk. MATERIALS AND METHODS 118 women and 98 men with type 2 diabetes mellitus who developed cancer after diagnosis of diabetes and the same number of strictly age matched controls with type 2 diabetes and without malignancy were included into the study. Diabetes duration, antidiabetic medications use, glycated hemoglobin level, body mass index, smoking habits, occupation, presence of comorbidities and aspirin use were included into analyses. CONCLUSIONS Metformin demonstrated protective effect against cancer in both sexes. Obesity and insulin treatment seem to have greater impact on cancer risk among women.

Glucose variability and glycated hemoglobin HbA1c in type 1 and type 2 diabetes

Introduction. The ultimate goal of diabetes therapy is to prevent chronic complications of the disease. HbA 1c level is closely related to the risk of development of micro- and macrovascular complications, however blood glucose variability (BGV) has emerged recently as yet another possible risk factor for vascular, particularly endothelial damage in diabetes. Continuous glucose monitoring systems (CGMS) are currently used for the BGV assessment, however due to their costs they are rarely utilised in daily clinical practice. The aim of the study was to assess BGV and its relationship with HbA 1c in patients with well (HbA 1c ∼7%) and poorly (HbA 1c ∼10%) controlled type 1 and type 2 diabetes. Material and methods. 131 patients subdivided in 4 groups according to diabetes type and level of metabolic control were enrolled into the study. All patients underwent continuous glucose monitoring with the use of iPRO2 system (Medtronic). Results. BGV was lower in type 2 than in type 1 diabetes patients. There was no statistically significant relationship between BGV and HbA 1c in well or poorly controlled patients with type 1 or type 2 diabetes. However, well controlled type 1 diabetes patients presented with greater degree of BGV than poorly controlled type 1 diabetes subjects. Conclusions. HbA 1c does not reflect blood glucose variability as assessed with CGMS in type 1 or type 2 diabetes subjects. BGV is significantly greater in type 1 diabetes than in type 2 diabetes, therefore the use CGMS might be of particular benefit for the former group of patients, especially those with good glycemic control.

Antidiabetic medications use and cancer risk in type 2 diabetes

Introduction. The risk of several types of cancer is increased in type 2 diabetes mellitus (T2DM). Impact of antidiabetic medications on this risk is still a matter of controversies. The aim of our observational study was to evaluate the risk of cancer occurrence associated with the most frequently used antidiabetic agents. Material and methods. 213 patients (118 women) with T2DM who developed cancer while treated for diabetes and 213 subjects with T2DM without cancer, matched by age and gender in a 1:1 case-control manner were included. Date of cancer diagnosis was considered as index time, and for each comparator data from the same calendar time were used. Results. Both in the univariate and in multiple logistic regression analysis metformin use was associated with reduced cancer risk, while elevated risk associated with insulin use was significant only in univariate but not in multiple logistic regression analysis. Insulin and sulfonylurea derivatives in monotherapy were associated with significantly higher cancer risk compared to metformin monotherapy, while in combination with metformin this risk was attenuated to non-significant level. Conclusion. Our study suggests protective effect of metformin and potentially negative impact of insulin and sulfonylurea derivatives on cancer risk. These findings should be interpreted with caution, due to relatively small study group. Nevertheless, to minimize cancer risk associated with antidiabetic medications’ use, metformin should be continued as long as medically acceptable and it should be combined with insulin or SU to neutralize risk associated with using either of the latter drugs in monotherapy.

The belief of control and engagement in health related behaviours in the groups of adolescents with type 1 diabetes and excess body weight

Introduction. The aim of this study is to assess the level of health-related behaviours among adolescents with type 1 diabetes and excess body weight, and the correlation occurring between the locus of control and the intensity of selected health-related behaviours among the respondents. Material and methods. The study was conducted among patients of the Diabetes Clinic of the University Clinical Hospital No. 1 in Lodz and the Outpatient Clinic for Obesity Prevention and Therapy, Polish Mother’s Memorial Hospital — Research Institute in Lodz. The age of the patients ranged from 12 to 20. The measurement of the variables was done utilising three methods: the Health Behaviour Inventory (IZZ), the Delta questionnaire to measure the locus of control and a survey of the author’s own design. Results. The results indicate, inter alia, that the surveyed young people suffering from type 1 diabetes or excess body weight do not engage in health-related behaviours more intensely than healthy individuals, though, the belief of having influence on their lives (the internal locus of control) dominates among them. What is more, a strong need for social approval is correlated, in the study groups, with the level of healthrelated behaviours, which can suggest that the average level of health-related behaviours stems from a desire to present oneself in a best possible light. Conclusion. Young people with type 1 diabetes and people with excess body weight present a comparable, unfortunately only average, level of health-related behaviours. Results suggest that the respondents probably tried to present themselves in a best possible light and the outcomes obtained, not higher than average, can be overstated, as compared with the actual level of health-related behaviours.

Time of onset of coronary artery disease in diabetic patients depends on genetic polymorphism in region 9p21 but not in 1p25

Introduction. Type 2 diabetes (T2DM) is an important risk factor for development of coronary artery disease (CAD) and its complications. Recent genetic studies revealed possible association between those two conditions on the genome level. In our study we analysed whether polymorphisms in loci 1q25 and 9p21, previously characterized as risk factors of CVD, have an influence on early-onset CAD in T2DM patients. Materials and methods. Our case-control study included 338 patients suffering from T2DM and CAD. For the study purpose the cohort was divided into two groups based on the age of CAD onset: case group with earlyonset CAD (< 55 for males and < 65 years for females, n = 180) and control group (≥ 55 and ≥ 65 years respectively, n = 158). Epidemiological data was taken from medical history and retrospective questionnaire; blood samples were collected. The rs2383206, rs1333049 and rs10911021 were genotyped using method of fluorescently labelled allele specific oligonucleotides. Results. Statistical analysis did not reveal any significant differences between two groups in the mean duration of diabetes, metabolic parameters (weight, waist circum- ference, frequency of obesity according to BMI, mean blood pressure or lipids levels) and smoking history. There were statistical differences between groups in family incidence of CAD (70.0% patients in cases vs. 45.6% in controls; p < 0.005), hypertension (77.1% vs. 47.8%; p < 0.005) and obesity (61.2% vs. 49.0%; p < 0.05). Genetic analysis revealed that frequency of the G allele of rs2383206 in 9p21 region was significantly higher in cases than in controls (62.4% vs 44.0% p < 0.00001). Homozygotes GG were 39.4% of cases and 18.8% in controls (p = 0.0001). The OR for increased risk of early CAD in GG homozygotes was 2.81, 95% CI: 2.39–3.24, after adjustment for conventional risk factors it was reduced to 2.58. There was statistically significantly higher frequency of GG homozygotes among patients with poor glycaemic control (HbA1c ≥ 7%; 41.3% vs. 15.9; p = 0.0011) and non-obese subjects (BMI < 30 kg/m2; 39.7% vs. 18.2%, p = 0.0002). Similar association between genotype and risk of early CAD was found for another polymorphism rs1333049 in 9p21 region. Frequency of allele C was significantly higher in cases than in controls (56.3% vs 43.4, p = 0.0036) and homozygotes CC were 31.6% in cases and 17.4% in controls (p = 0.0083). OR for this association was 2.2 (95% CI: 1.83–2.56); after adjustments 1.96. We didn’t find any association between genotypes distribution of rs10911021 and early onset of CAD. Conclusions. Our findings clearly suggest that polymorphisms in 9p21 region have an influence on development of early-onset CAD in T2DM, especially in non-obese patients and subjects with poor glycaemic control. (Clin Diabet 2016; 5, 1: 7–14)