Mykola Khalangot

Body mass index and the risk of total and cardiovascular mortality among patients with type 2 diabetes: a large prospective study in Ukraine

Background: Several prospective studies have evaluated the association between body mass index (BMI) and cardiovascular mortality among patients with type 2 diabetes; however, the results are controversial. Objective: To investigate the association of different BMI distributions with total and cardiovascular mortality among diabetic patients. Methods: A total of 30 534 Ukrainian men and 58 909 women with type 2 diabetes from the nationwide population-based diabetes register were included in this study. Results: During a mean follow-up of 2.7 years, 7804 deaths were recorded, of which 3320 were due to cardiovascular disease. After adjustment for age, smoking and alcohol drinking, the hazard ratios across the five BMI categories (<23, 23–24.9, 25–29.9 (reference group), 30–34.9 and ⩾35 kg/m2) among diabetic men were 1.57 (95% CI 1.42 to 1.74), 1.16 (1.05 to 1.28), 1.0, 1.01 (0.91 to 1.12) and 1.24 (1.02 to 1.50) for total mortality, and 1.67 (95% CI 1.42 to 1.95), 1.30 (1.12 to 1.51), 1.0, 1.13 (0.96 to 1.34) and 1.54 (1.16 to 2.05) for cardiovascular mortality, respectively. The respective hazard ratios among diabetic women were 1.34 (95% CI 1.22 to 1.47), 1.00 (0.91 to 1.10), 1.0, 1.04 (0.97 to 1.12) and 1.27 (1.14 to 1.41) for total mortality, and 1.36 (95% CI 1.18 to 1.57), 1.06 (0.92 to 1.21), 1.0, 1.12 (1.01 to 1.25) and 1.35 (1.15 to 1.59) for cardiovascular mortality. Additional adjustment for systolic blood pressure, total cholesterol, history of cardiovascular disease, diabetes treatments and duration of diabetes affected the results only slightly. Conclusions: This study indicated a U-shaped association between BMI and total and cardiovascular mortality among diabetic men and women.

Glibenclamide-related excess in total and cardiovascular mortality risks: Data from large Ukrainian observational cohort study

OBJECTIVE To compare mortality risks among type 2 diabetes (T2D) patients being treated with glibenclamide, gliclazide, or glimepiride. METHODS Retrospective observational cohort studies of primary care-based diabetes register were carried out. Risk of total and cardiovascular (CVD) mortality was evaluated in cohort of T2D patients that were treated with either glibenclamide (n=50,341), glimepiride (n=2479) or gliclazide (n=11,368). Cox regression was used for multifactor evaluation. A cross-sectional evaluation of oral anti-diabetic drug (OAD) structure for 2005 and 2007 was also performed, as well as age at the time of death was compared in the timeframe between 2002 and 2007. RESULTS Total mortality was lower for gliclazide and glimepiride, vs. glibenclamide cohort: HRs 0.33 (95% CI 0.26-0.41), p<0.001 and 0.605 (95% CI 0.413-0.886), p<0.01 respectively. CVD mortality risk reduction vs. glibenclamide was significant only in gliclazide cohort: 0.29 (95% CI 0.21-0.38), p<0.001. Glibenclamide prescriptions had changed from 64.0% (95% CI 63.5-64.5) to 59.5% (95% CI 9.7-10.4). Age at the time of death for OAD-treated patients increased by 6.27 (95% CI 3.67-8.87)yrs, p<0.001. CONCLUSION Glibenclamide treatment of T2D is associated with greater risk of all-cause mortality, vs. gliclazide or glimepiride treatment, and CVD mortality, vs. gliclazide treatment.

Primary care diabetes in Ukraine.

People with diabetes in Ukraine are cared for by endocrinology specialists. Implementation of the National Diabetes Plan solved the problem of free insulin supply. However, many problems of diabetic care, including increase of accessibility to some laboratory tests and treatments, are still unresolved. An increase of life expectancy among diabetic patients has been noted during the past 5 years.

The European EUCCLID pilot study on care and complications in an unselected sample of people with type 2 diabetes in primary care.

BACKGROUND European studies on quality of diabetes care in an unselected primary care diabetes population are scarce. RESEARCH QUESTION To test the feasibility of the set-up and logistics of a cross-sectional EUropean study on Care and Complications in patients with type 2 diabetes (T2DM) in Primary Care (EUCCLID) in 12 European countries. METHOD One rural and one urban practice from each country participated. The central coordinating centre randomly selected five patients from each practice. Patient characteristics were assessed including medical history, anthropometric measures, quality indicators, UKPDS-risk engine, psychological and general well-being. RESULTS We included 103 participants from 22 GPs in 11 countries. Central data and laboratory samples were successfully collected. Of the participants 54% were female, mean age was 66 years and mean duration of diabetes was 9.6 years. Besides, 18% were using insulin, 31% had a history of cardiovascular disease, mean HbA1c was 7.1% (range 6.6-8.0), mean systolic blood pressure was 133.7 mmHg (range 126.1-144.4) and mean total cholesterol was 4.9 mmol/l (range 4.0-6.2). CONCLUSION A European study on care and complications in a random selection of people with T2DM is feasible. There are large differences in indicators of metabolic control and wellbeing between countries.

Gender risk of nonfatal stroke in type 2 diabetic patients differs depending on the type of treatment.

BACKGROUND The gender differences in stroke risk among diabetic patients with different treatments have not been studied previously. We aim to determine if there is a gender difference in nonfatal stroke risk in diabetic patients receiving different types of glucose-lowering treatments. METHODS In December 2005, data of type 2 diabetic patients were extracted from a nationwide population-based diabetes registry covering 11 Ukrainian regions. Male/female odds ratios (OR) for nonfatal stroke were calculated in three treatment groups: diet only 7,273/15,901, oral glucose-lowering drugs 15,109/33,913, and insulin 5,529/12,462 male/female. Male/female ORs of stroke were estimated using a logistic regression model. RESULTS The age-adjusted ORs of stroke were higher among diabetic men compared with diabetic women with oral glucose-lowering drug treatment (OR 1.37, 95% CI 1.22-1.54) and diet treatment only (OR 1.53, 95% CI 1.35-1.73). No differences were found among patients who used insulin (OR 0.97, 95% CI 0.84-1.11). Further adjustment for duration of type 2 diabetes, body mass index (BMI), systolic blood pressure, total cholesterol, and smoking affected the results only slightly. CONCLUSIONS The gender risks of nonfatal stroke in patients with type 2 diabetes appear to differ considerably depending on treatment types.

The joint effects of different types of glucose-lowering treatment and duration of diabetes on total and cardiovascular mortality among subjects with type 2 diabetes

OBJECTIVE To compare the joint effects of different types of glucose-lowering treatment (oral drugs, insulin, and both) and duration of diabetes on total and cardiovascular mortality among diabetic patients. METHODS Study cohorts included 30,534 Ukrainian males and 58,909 females with type 2 diabetes. During the mean follow-up of 2.7 years, 7804 deaths were recorded. RESULTS The multivariate-adjusted hazard ratios (HRs) for total mortality among diabetic patients, who used oral glucose-lowering drug (OGLD) only, insulin only, both insulin and OGLD, were 1.00, 2.34, and 2.22 in men, and 1.00, 2.12, and 2.20 in women, respectively. The multivariate-adjusted HRs for total mortality across categories of duration of diabetes (<5, 5-9, 10-14, 15-19, and >/=20 years) were 1.00, 1.17, 1.32, 1.43, and 1.57 (p(trend)<0.001) in men, and 1.00, 1.13, 1.34, 1.74, and 1.68 (p(trend)<0.001) in women, respectively. Diabetic patients who used insulin and reported longer duration of diabetes had the highest risk of total mortality. CONCLUSION Type 2 diabetic patients treated with insulin show a greater risk of death than those treated with OGLD only. Increasing duration of diabetes is associated with an increased death risk. The combination of insulin treatment and longer duration of diabetes identifies a particular high death risk.

Leukocyte telomere length is inversely associated with post-load but not with fasting plasma glucose levels

Type 2 diabetes mellitus is characterized by shorter leukocyte telomere length, but the relationship between leukocyte telomere length and type 2 diabetes mellitus development is rather questioned. Fasting and post-load glycaemia associated with different types of insulin resistance and their relation with leukocyte telomere length remains unknown. We compared leukocyte telomere length and fasting or post-load glucose levels in persons who do not receive glucose lowering treatment. For 82 randomly selected rural residents of Ukraine, aged 45+, not previously diagnosed with type 2 diabetes mellitus, the WHO oral glucose tolerance test and anthropometric measurements were performed. Leukocyte telomere length was measured by standardized method of quantitative monochrome multiplex polymerase chain reaction in real time. Spearman’s or Pearson’s rank correlation was used for correlation analysis between fasting plasma glucose or 2-h post-load plasma glucose levels and leukocyte telomere length. Logistical regression models were used to evaluate risks of finding short or long telomeres associated with fasting plasma glucose or 2-h post-load plasma glucose levels. No association of fasting plasma glucose and leukocyte telomere length was revealed, whereas 2-h post-load plasma glucose levels demonstrated a negative correlation (P < 0.01) with leukocyte telomere length. Waist circumference and systolic blood pressure were negatively related (P = 0.03) with leukocyte telomere length in men. Oral glucose tolerance test result-based glycemic categories did not show differences between mean leukocyte telomere length in categories of normal fasting plasma glucose and 2-h post-load plasma glucose (NGT, n = 33); diabetes mellitus (DM), n = 18 and impaired fasting glucose/tolerance (IFG/IGT, n = 31) levels. A correlation relationship between leukocyte telomere length and 2-h post-load plasma glucose level in NGT; IFG/IGT and DM groups (P = 0.027; 0.029 and 0.049, respectively) was revealed; the association between leukocyte telomere length and fasting plasma glucose was confirmed in DM group only (P = 0.009). Increase of 2-h post-load plasma glucose (but not fasting plasma glucose) level improves the chances of revealing short telomeres: OR 1.52 (95% CI 1.04–2.22), P = 0.03. After the adjustment for age, gender, waist circumference, systolic blood pressure, and fasting plasma glucose, these phenomena remain significant. We conclude that 2-h post-load plasma glucose but not fasting plasma glucose is inversely associated with leukocyte telomere length. Impact statement • Contradictory epidemiologic data have been obtained about the link between the leucocyte telomere length (LTL) and diabetes. Type 2 diabetes (T2D) is likely to be pathophysiologically heterogeneous, but comparison of the association of LTL separately with fasting plasma glucose (FPG) and 2-h post-load plasma glucose (2hPG) levels has not been done before. Thus, the study of LTL changes associated with different types of hyperglycaemia, that largely determine the heterogenity of T2D is important. • In a population-based study of rural Ukrainians, we were the first to demonstrate that the increase of 2hPG (but not FPG) level increases the chances of revealing short telomeres. • The obtained data can help to clarify the relationship between the LTL shortening and different conditions of the insulin resistance (mainly liver resistance in high FPG and mostly muscle and adipose tissue resistance in high 2hPG).

Glucose Tolerance Testing and Anthropometric Comparisons Among Rural Residents of Kyiv Region: Investigating the Possible Effect of Childhood Starvation—A Community-Based Study:

A relationship between childhood starvation and type 2 diabetes mellitus (T2D) in adulthood was previously indicated. Ukraine suffered a series of artificial famines between 1921 and 1947. Famines of 1932 to 1933 and 1946 were most severe among them. Long-term health consequences of these famines remain insufficiently investigated. Type 2 diabetes mellitus screening was conducted between June 2013 and December 2014. A total of 198 rural residents of Kyiv region more than 44 years of age, not registered as patients with T2D, were randomly selected. In all, 159 persons answered the question about starvation of parental family, including 73 born before 1947. Among them, 62 persons answered positive. Anthropometric measurements and glucose tolerance tests were performed. A logistic regression model was used to evaluate results. Type 2 diabetes mellitus was detected in 7 of 62 persons (11.3%), who starved during childhood vs 6 of 11 (54.5%) who did not (P = .002), age-adjusted and sex-adjusted odds ratio (OR) (95% confidence interval): 0.063 (0.007-0.557). Analysis of the anthropometric data revealed a negative connection between adulthood height and neck circumference (cm, continued variables) and childhood starvation: age-adjusted and sex-adjusted ORs 0.86 (0.76-0.97) and 0.73 (0.54-0.97), respectively. Individuals who starved during famines of 1932 to 1933 and 1946 in Ukraine had a decreased T2D prevalence several decades after the famine episodes.

Prevalence of Type 1 Diabetes Correlates with Daily Insulin Dose, Adverse Outcomes and with Autoimmune Process Against Glutamic Acid Decarboxylase in Adults

The territorial differences in the prevalence of type 1 diabetes mellitus (T1D) around the world were previously reported (Amos et al., 1997; Green & Patterson, 2001; Levy-Marchal, 2001), but the data were based on the study of juvenile T1D epidemiology, i.e., in patients diagnosed with T1D before the age of 15 years. These data became the basis for the epidemiological evaluation of the whole T1D patient population. With the relatively limited number of children with T1D within the current territory, less effort is required for data gathering. Besides, as the age increases, it becomes more difficult to relate a diabetic condition to a certain diabetes type (Keen, 1998), thus, making it impossible to directly use the diabetes-type data obtained from Primary Care. In modern epidemiological studies, the key data concern the age at the time of the diagnosis—patients who were diagnosed before the age of 30 years and are insulin-treated, are considered to suffer from T1D.