Long-term impact of pre-natal exposure to the Ukraine famine of 1932-1933 on adult type 2 diabetes mellitus.

Importance: The long-term impacts of early-life famine exposure on Type 2 Diabetes Mellitus (T2DM) have been widely documented across countries, but it remains less clear what is the critical time window and if there is a dose-response between famine intensity and risk of T2DM. Objective: To establish the relation between prenatal famine exposure and adult Type 2 diabetes mellitus (T2DM). Design: A national cross-sectional study. Setting: The man-made Ukrainian Holodomor famine of 1932-1933. Participants: A total number of 128,225 T2DM cases diagnosed at age 40 or over from the national diabetes register 2000-2008 in Ukraine. The population at risk includes 10,186,016 Soviet Ukraine births (excepting one oblast/province) between 1930-1938 classified by month and year and oblast of birth. Exposure: Births born in January-June 1934 from oblasts that experienced extreme, severe, or significant famine in 1932-1933. Famine intensity was measured based on the excess mortality during the famine. Main Outcomes and Measures: T2DM diagnosis was based on WHO (1999) criteria. Results: We observed in univariate analysis a 1.8-fold increase in T2DM (OR 1.80; 95% CI 1.74-1.85) among individuals born in the first half-year of 1934 in regions with extreme, severe, or significant famine. We observed no increase among individuals born in regions with no famine. In multivariate analysis across regions and adjusting for season of birth we observed a larger than 2-fold increase (OR 2.21; 95% CI 2.00-2.45). There was a dose-response by famine intensity, with ORs increasing from 1.94 to 2.39 across regions. The pattern was similar in men and women. Conclusions and Relevance: Births in the first half-year of 1934 were conceived at the height of the Ukraine famine in 1933. This relation for T2DM outcomes points to early gestation as a critical time window relating maternal nutrition in pregnancy to offspring health in later life. Further studies of biological mechanisms should focus on this time window for which changes in DNA methylation and later body size have also been observed.

RAAS inhibitors are associated with a better chance of surviving of inpatients with Covid-19 without a diagnosis of diabetes mellitus, compared with similar patients who did not require antihypertensive therapy or were treated with other antihypertensives.

Purpose: The effect of renin-angiotensin-aldosterone system (RAAS) inhibitors in combination with COVID-19 and diabetes mellitus (DM) remains unknown. We assessed the risk of death in COVID-19 inpatients based on the presence or absence of DM, arterial hypertension (AH) and the use of RAAS inhibitors or other antihypertensives. Methods: The results of treatment of all adult PCR-confirmed COVID-19 inpatients (n = 1097, women 63.9%) from 02/12/2020 to 07/01/2022 are presented. The presence of DM at the time of admission and the category of antihypertensive drugs during hospital stay were noted. Leaving the hospital due to recovery or death was considered as a treatment outcome. Multivariable logistic regression analysis was used to assess the risk of death. Patients with COVID-19 without AH were considered the reference group. Results: DM was known in 150 of 1,097 patients with COVID-19 (13.7%). Mortality among DM inpatients was higher: 20.0% vs. 12.4% respectively (p=0.014). Male gender, age, fasting plasma glucose (FPG) and antihypertensives were independently associated with the risk of dying in patients without DM. In DM group such independent association was confirmed for FPG and treatment of AH. We found a reduction in the risk of death for COVID-19 inpatients without DM, who received RAAS inhibitors compared with the corresponding risk of normotensive inpatients, who did not receive antihypertensives: OR 0.22 (95% CI 0.07-0.72) adjusted for age, gender and FPG. Conclusion: This result raises a question about the study of RAAS inhibitors effect in patients with Covid-19 without AH.

Metabolic and Anthropometric Parameters of Persons at Risk of Developing Type 2 Diabetes Mellitus Before and After 3 Months of Consuming Insoluble Dietary Fiber.

Background: Observational studies have shown that insoluble fiber (IF) can be effective in preventing type 2 diabetes (T2D), but there is a lack of experimental data on the effect of short-term consumption of IF on metabolic parameters. We tried to investigate whether there was an improvement in glycemia and body composition in individuals at risk for T2D after 3 months of IF consumption. Methods: This "Type 2 Diabetes Mellitus Prevention Ukraine (T2DPUA)" study describes participants with impaired fasting glucose (IFG) as determined by ADA criteria. The study involved 30 people, including 21 women (70%). Daily, 15 g of IF derived from wheat was used. T2DPUA did not have a placebo group and the intervention lasted 3 months. Evaluation of fasting plasma glucose (FPG) and 2h plasma glucose (2hPG), glycated hemoglobin (HbA1c), total cholesterol, HDL-cholesterol, triacylglycerols, uric acid, and γ-glutamyl transferase was performed. The baseline and 3-monthly anthropometric examinations included measurements of weight, waist and hip circumference. Fat mass was assessed by bioelectrical impedance analysis. Paired samples t-test or Wilcoxon test were used. Result: A decrease of FPG (P = .042), HbA1c (P < .001), 2hPG (P = .005), weight (P < .001), body mass index (P < .001), the proportion of body fat (P = .006), and the absolute amount of fat (P < .001), increases in systolic (P < .001) and diastolic (P = .008) blood pressure was shown. The number of people with hypertension did not change. The absolute amount of body fat decreased by almost 5% and tolerance to the standard glucose load improved by 15%. The dynamics of other metabolic parameters were not revealed. Conclusion and Recommendation: Data about improvement of glycemia and body composition over a short period of using IF by individuals with IFG are new and deserve larger studies.

Neuronal Dysfunction Is Linked to the Famine-Associated Risk of Proliferative Retinopathy in Patients With Type 2 Diabetes.

Persons with type 2 diabetes born in the regions of famine exposures have disproportionally elevated risk of vision-threatening proliferative diabetic retinopathy (PDR) in adulthood. However, the underlying mechanisms are not known. In the present study, we aimed to investigate the plausible molecular factors underlying progression to PDR. To study the association of genetic variants with PDR under the intrauterine famine exposure, we analyzed single nucleotide polymorphisms (SNPs) that were previously reported to be associated with type 2 diabetes, glucose, and pharmacogenetics. Analyses were performed in the population from northern Ukraine with a history of exposure to the Great Ukrainian Holodomor famine [the Diagnostic Optimization and Treatment of Diabetes and its Complications in the Chernihiv Region (DOLCE study), n = 3,583]. A validation of the top genetic findings was performed in the Hong Kong diabetes registry (HKDR, n = 730) with a history of famine as a consequence of the Japanese invasion during WWII. In DOLCE, the genetic risk for PDR was elevated for the variants in ADRA2A, PCSK9, and CYP2C19*2 loci, but reduced at PROX1 locus. The association of ADRA2A loci with the risk of advanced diabetic retinopathy in famine-exposed group was further replicated in HKDR. The exposure of embryonic retinal cells to starvation for glucose, mimicking the perinatal exposure to famine, resulted in sustained increased expression of Adra2a and Pcsk9, but decreased Prox1. The exposure to starvation exhibited a lasting inhibitory effects on neurite outgrowth, as determined by neurite length. In conclusion, a consistent genetic findings on the famine-linked risk of ADRA2A with PDR indicate that the nerves may likely to be responsible for communicating the effects of perinatal exposure to famine on the elevated risk of advanced stages of diabetic retinopathy in adults. These results suggest the possibility of utilizing neuroprotective drugs for the prevention and treatment of PDR.

Relationship between hyperglycemia, waist circumference, and the course of COVID-19: Mortality risk assessment.

An observational study was conducted in Ukraine to determine the independent mortality risks among adult inpatients with COVID-19. The results of treatment of COVID-19 inpatients (n = 367) are presented, and waist circumference (WC) was measured. Logistic regression analysis was applied to evaluate the effects of factors on the risk of mortality. Odds ratios and 95% CIs for the association were calculated. One hundred and three of 367 subjects had fasting plasma glucose level that met the diabetes mellitus criteria (≥7.0 mmol/L), in 53 patients, diabetes mellitus was previously known. Two hundred and eleven patients did not have diabetes or hyperglycemia. Diabetes mellitus/hyperglycemia odds ratio 2.5 (CI 1.0-6.1), p = 0.045 loses statistical significance after standardization by age, waist circumference or fasting plasma glucose. No effect on gender, body mass index-determined obesity, or hypertension was found. The fasting plasma glucose (>8.5 mmol/L), age (≥61 years), and waist circumference (>105 cm) categories were associated with ORs 6.34 (CI 2.60-15.4); 4.12 (CI 1.37-12.4); 8.93 (CI 3.26-24.5), respectively. The optimal model of mortality risk with AUC 0.86 (CI 0.81-0.91) included the diabetes/heperglycemia and age categories as well as waist circumference as a continued variable. Waist circumference is an independent risk factor for mortality of inpatients with COVID-19.

Perinatal famine is associated with excess risk of proliferative retinopathy in patients with type 2 diabetes.

PURPOSE: Intrauterine undernutrition is associated with increased risk of type 2 diabetes. Children born premature or small for gestational age were reported to have abnormal retinal vascularization. However, whether intrauterine famine act as a trigger for diabetes complications, including retinopathy, is unknown. The aim of the current study was to evaluate long-term effects of perinatal famine on the risk of proliferative diabetic retinopathy (PDR). METHODS: We studied the risk for PDR among type 2 diabetes patients exposed to perinatal famine in two independent cohorts: the Ukrainian National Diabetes Registry (UNDR) and the Hong Kong Diabetes Registry (HKDR). We analysed individuals born during the Great Famine (the Holodomor, 1932-1933) and the WWII (1941-1945) famine in 101 095 (3601 had PDR) UNDR participants. Among 3021 (251 had PDR) HKDR participants, we studied type 2 diabetes patients exposed to perinatal famine during the WWII Japanese invasion in 1942-1945. RESULTS: During the Holodomor and WWII, perinatal famine was associated with a 1.76-fold (p = 0.019) and 3.02-fold (p = 0.001) increased risk of severe PDR in the UNDR. The risk for PDR was 1.66-fold elevated among individuals born in 1942 in the HKDR (p < 0.05). The associations between perinatal famine and PDR remained statistically significant after corrections for HbA1c in available 18 507 UNDR (padditive interaction < 0.001) and in 3021 HKDR type 2 diabetes patients (p < 0.05). CONCLUSION: In conclusion, type 2 diabetes patients, exposed to perinatal famine, have increased risk of PDR compared to those without perinatal famine exposure. Further studies are needed to understand the underlying mechanisms and to extend this finding to other diabetes complications.

Trends in the incidence of diagnosed diabetes: a multicountry analysis of aggregate data from 22 million diagnoses in high-income and middle-income settings.

BACKGROUND: Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. METHODS: In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995-2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. FINDINGS: Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from -1·1% to -10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. INTERPRETATION: The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Telomere length in different metabolic categories: Clinical associations and modification potential.

IMPACT STATEMENT: Metabolic disorders are known to be associated with accelerated telomere attrition. Their pathophysiological heterogeneity suggests the importance of multiple tests in examining these associations. However, oral glucose tolerance test (OGTT) has rarely been performed in such studies to date. There are few studies aimed at determining leukocyte telomere length (LTL) in different categories of impaired glucose tolerance (IGT), and those that do exist do not take into account the impaired fasting glucose (IFG)/IGT categorization. Therefore, we believe our study, when the OGTT was used, is important to the field. This testing made it possible to determine whether LTLs are associated with glucose levels in different hyperglycemic categories. Our data indicate that relationships between LTLs and IFG/IGT levels are not the same. This distinction can potentially be used in categorization of metabolic disorders and in determining the effectiveness of interventions aimed at treating diabetes and other metabolic abnormalities.

Evaluation of type 2 diabetes prevention through diet modification in people with impaired glucose regulation: A population-based study.

PURPOSE: A few interventional studies to date have specifically assessed the association between dairy products and/or sugar consumption and the risk of type 2 diabetes mellitus (T2D) incidence. The aim of this study was to assess the effectiveness of diet modification in people with impaired glucose regulation (IGR) as defined by a glucose tolerance test (GTT). METHODS: A quasi-experimental study design was used for this study. A total of 318 randomly selected 18-year-old or older participants from the rural area of the Kyiv region of Ukraine who had not been registered as T2D patients before underwent GTT between June 2013 and June 2017. For those who had been diagnosed with IGR, World Health Organization (WHO)/International Diabetes Federation criteria were used. Of 318 participants screened for T2D, 123 (74% of them females) were diagnosed with IGR. They were aged 18 to 79 years old with a median (QI - QIII) age of 62 (52-68) years. They were repeatedly tested during the study and completed a questionnaire on average 2.8 (1.1) years (standard deviation [SD]), after they had received their lifestyle-based T2D prevention recommendations. In addition to basic recommendations, they were advised to consume approximately 200 g of low-fat dairy products and less than 25 g of sugar daily. Cases of screen-detected diabetes mellitus (SDDM) were diagnosed and reported as an outcome variable if a fast capillary blood glucose level reached 6.1 mmol/L and above. To define the association between implementation of recommendations and the risk of SDDM, the Cox proportional-hazards regression analysis was used. RESULTS: During the study observation period, 56 (45.5%) of 123 IGR-positive participants were recognized as SDDM cases. Those individuals with IGR (n = 111) who confirmed their adherence to preventive recommendations had a significantly lower risk of identifying SDDM, age- and gender-adjusted hazard ratio (HR) 0.26 (95% CІ; 0.09-0.72). This effect appears to be related to the recommendation to reduce the daily intake of sugar to less than 25 g (n = 99), corresponding to age- and gender-adjusted HR 0.44 (95% CІ; 0.2-0.99). We cannot prove that increasing consumption of dairy products, vegetables, and fruit or increased physical activity had similar effectiveness. CONCLUSIONS: After 2.8 years of follow-up, the individuals who are IGR-positive and who confirmed their adherence to lifestyle-based preventive recommendations had a significantly lower risk of identifying SDDM. This effect appears to be related to recommendations to reduce the daily intake of sugar to less than 25 g.

Additional Impact of Glucose Tolerance on Telomere Length in Persons With and Without Metabolic Syndrome in the Elderly Ukraine Population.

Rationale: Association between different components of metabolic syndrome and the rate of age-related telomere shortening was reported repeatedly, although some findings are inconsistent across studies, suggesting the need for further research on the topic. In the present study, we examined relationships between different components of metabolic syndrome (MetS); glucose tolerance reflected in 2-h post-load plasma glucose (2hPG) levels and age on the leukocyte telomere length (LTL) in Ukraine population. Methods: The study was conducted on the 115 adult individuals residing in the Kyiv region (Ukraine). Among them, 79 were diagnosed with MetS according to the International Diabetes Federation definition. LTL were determined by a qPCR-based method. Multivariate logistic regression (MLR) and artificial neural networks (ANN) modeling were used for the analysis of the results. ROC-analysis was also performed to compare the predictively values of this models. Results: MetS was associated with a high (OR = 3.0 CI 1.3-6.7; p = 0.01) risk of having shorter telomeres that remained significant after adjusting for age, gender and 2hPG levels. Fasting plasma glucose (FPG) levels and other MetS components did not affect the magnitude of the relationship and did not reveal the independent influence of these factors. The level of 2hPG in turn, demonstrated a significant relationship (OR = 1.3 CI 1.0-1.6 per 1 mmol/l; p = 0.04) with LTL regardless of the presence of MetS. The non-linearity of the interactions between age, gender and 2hPG level was revealed by neural network modeling (AUC = 0.76 CI 0.68-0.84). Conclusion: Our study found that impaired glucose tolerance, but not FPG levels, affected the association between LTL and MetS, which may be also indicative for pathophysiological differences in these hyperglycemia categories. 2hPG levels can provide an opportunity for a more accurate diagnostics of MetS and for evaluating the rate of aging in patients with MetS. Further research, however, is needed to verify this assumption.

Hyperglycemia attenuates the association between telomere length and age in Ukrainian population.

Diabetes-related conditions such as chronic hyperglycemia and related oxidative stress and inflammation were repeatedly associated with accelerated telomere shortening in epidemiological studies, although some findings are inconsistent. In present study, we aimed to assess the impact of disturbances in glucose metabolism on association between age and leukocyte telomere length (LTL) in the Ukrainian population. The study was conducted on the 119 adult subjects aged between 43 and 87 years residing in the Kyiv region, Ukraine. LTL was determined by a quantitative PCR-based method. LTL was negatively correlated with the measure of abdominal obesity such as waist-hip ratio, as well as with both fasting plasma glucose (FPG) and two-hour post-load glucose (2hPG) levels. Consistently with previous studies, a significant negative association between LTL and age was observed in individuals with normal (<5.6 mmol/L) FPG levels. Unexpectedly, however, no association was found in subjects with impaired glucose metabolism assessed by abnormal FPG or/and 2hPG levels. No association between LTL and age was observed in a logistic regression model; the association between LTL and age became significant after adjusting for FPG level. In the FPG-adjusted model, 1.6-time lower odds to have long telomere length were indicated for each 10 years increase in age. We hypothesize that the attenuation of association between LTL and age in hyperglycemic persons can likely be attributed to the interaction of multidirectional processes determining this relationship.

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.

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).

Association between type 2 diabetes and prenatal exposure to the Ukraine famine of 1932-33: a retrospective cohort study.

BACKGROUND: The effect of fetal and early childhood living conditions on adult health has long been debated, but empirical assessment in human beings remains a challenge. We used data from during the man-made Ukrainian famine of 1932-33 to examine the association between restricted nutrition in early gestation and type 2 diabetes in offspring in later life. METHODS: We included all patients with type 2 diabetes diagnosed at age 40 years or older in the Ukraine national diabetes register 2000-08, and used all individuals born between 1930 and 1938 from the 2001 Ukraine national census as the reference population. This study population includes individuals born before and after the famine period as controls, and those from regions that experienced extreme, severe, or no famine. We used prevalence odds ratios (ORs) as the measure of association between type 2 diabetes and early famine exposure, with stratification by region, date of birth, and sex for comparisons of diabetes prevalence in specific subgroups. FINDINGS: Using these two datasets, we compared the odds of type 2 diabetes by date and region of birth in 43,150 patients with diabetes and 1,421,024 individuals born between 1930 and 1938. With adjustment for season of birth, the OR for developing type 2 diabetes was 1·47 (95% CI 1·37-1·58) in individuals born in the first half of 1934 in regions with extreme famine, 1·26 (1·14-1·39) in individuals born in regions with severe famine, and there was no increase (OR 1·00, 0·91-1·09) in individuals born in regions with no famine, compared with births in other time periods. Multivariable analyses confirmed these results. The associations between type 2 diabetes and famine around the time of birth were similar in men and women. INTERPRETATION: These results show a dose-response relation between famine severity during prenatal development and odds of type 2 diabetes in later life. Our findings suggest that early gestation is a critical time window of development; therefore, further studies of biological mechanisms should include this period. FUNDING: Ukraine State Diabetes Mellitus Program, US National Institutes of Health.

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.

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.