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AIMS: To investigate the effect of sulphonylurea (SU) treatment on all-cause and cardiovascular mortality as compared with metformin (MET), when used in combination with insulin (INS) in type 2 diabetes. METHODS: All type 2 diabetes patients aged ≥40 years were included at their first prescription of INS+MET or INS+SU, during 2001-2008. They were considered at risk until death or December 31st, 2011. Mortality rates were calculated per 1000 person-years. Crude and adjusted rate ratios (RR) were calculated using time dependent analysis with INS+MET as reference. RESULTS: There were 7122 patients (60.8% women) included in the analysis, with a mean age at baseline of 62.0±9.9 years. During the 11 years of study, patients on INS+MET contributed 13620 person-years and 330 deaths (mortality rate 24, CI95% 22-27), while those on INS+SU contributed 8720 person-years and 393 deaths (mortality rate 45, CI95% 41-50). Adjusted all-cause mortality RR were: SU 1.6 (CI95% 1.21-2.11, p<0.001), glimepiride 1.18 (CI95% 0.73-1.91, p=0.51), gliclazide 1.78 (CI95% 1.07-2.95, p=0.024), glibenclamide 1.66 (CI95% 0.71-3.88, p=0.23), glipizide 1.24 (CI95% 0.68-2.27, p=0.49), and gliquidonum 2.32 (CI95% 1.54-3.50, p=0.001). CONCLUSIONS: When combined with insulin as dual therapy, patients treated with SU were at increased mortality risk as compared with insulin + MET.

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AIM: To investigate the historical changes in survival with diabetes in elderly people with diabetes. RESEARCH DESIGN AND METHODS: We analyzed 6504 deaths (44.5% males) registered in a large urban population, aged ≥65 years, and deceased between 1943 and 2009. We split the analysis into three time periods according to year of death: 1943-1965, 1966-1988 and 1989-2009. The parallel changes in the corresponding general population were available. RESULTS: The mean age at diabetes onset was 70.8 ± 4.7 years, with mean disease duration at death 7.5 ± 5 years, and mean age at death 78.3 ± 5.9 years. The mean survival loss due to diabetes (expected minus observed survival) was 4.5 ± 5.1 years (4.9 ± 5.1 years for females versus 4.1 ± 5.2 years for males, p<0.001). The mean disease duration at death was 6.4 ± 5.7 years in the period 1943-1965, followed by a significant (p=0.019) rise to 7 ± 5 years in 1966-1988, and 8.3 ± 4.9 years (p<0.001) in 1989-2009. There was a significant increase in coronary heart disease and stroke, and a significant decrease in infections and end-stage renal disease as causes of death. CONCLUSIONS: We found a significant increase in age at onset and survival with diabetes leading to a significant increase in age at death. Females had a higher survival loss due to diabetes compared with males.

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AIMS: To investigate the major aspects of mortality in patients with noninsulin-treated type 2 diabetes mellitus (T2DM), from 1942 till 2000. SUBJECTS AND METHODS: We performed a retrospective study in 9698 noninsulin-treated T2DM patients, 5001 (51.6%) males and 4695 (48.4%) females, registered in Bucharest Diabetes Center and deceased between 1943 and 2000. For each patient the age at diabetes onset, disease duration, age at death, cause of death, sex, height and weight were recorded. RESULTS: The mean age at diabetes onset was 58.3 +/- 9.1 years in 1943-1960 period (no significant differences by sex) and 60.6 +/- 10.3 years in 1981-2000 (59.3 +/- 10.3 years in males and 61.8 +/- 10.1 years in females, p < 0.01 vs. males). The mean disease duration at death was 7.7 +/- 5.2 years in 1943-1960 period (no significant differences by sex) and 11.3 +/- 8.1 years in 1981-2000 (11.9 +/- 8.4 years in males and 10.7 +/- 7.6 years in females, p < 0.01 vs. males). The mean age at death was 66 +/- 9.8 years in 1943-1960 period (no significant differences by sex) and 71.9 +/- 9.7 years in 1981-2000 (71.2 +/- 9.9 years in males and 72.5 +/- 9.5 years in females, p < 0.01 vs. males). In the Cox regression analysis, an increase in mortality was associated with the masculine sex--9.6% (CI 95% 1-19%, p = 0.028) compared with feminine sex; 1 year increase in age at onset--4.8% (CI 95% 4.3-5.3%, p < 0.01); 1 kg/m2 increase in body mass index--2.9% (CI 95% 1.9-3.8%, p < 0.01); 1 mg/dl increase in mean fasting blood glucose--0.1% (CI 95% 0-0.2%, p = 0.025). The major causes of death in noninsulin-treated T2DM patients in the 1981-2000 period were: ischemic heart disease (53.8%), stroke (14.4%), cancer (9%), digestive diseases (6.3%), diabetes (5.3%), end stage renal disease (4.6%), infections (2.7%), diabetes coma (2.2%) and others (1.7%). CONCLUSIONS: There is a statistically significant increase in the proportion of death caused by ischemic heart disease, while infections significantly decreased in importance during the study period. The masculine sex, age at onset, mean fasting blood glucose and body mass index were all significant predictors of mortality in the Cox regression analysis, adjusted for the year of death.

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BACKGROUND AND AIMS: C reactive protein (CRP), a non-specific acute phase reactant, has been associated with multiple patogenic mechanisms involved in chronic illnesses, but up to now the significance of CRP in the postprandial state in diabetes mellitus has not been addressed. MATERIAL AND METHODS: We evaluated 58 type 2 diabetic patients (33F/25 M) with associated metabolic syndrome. The main characteristics of the patients were: age 58.1+/-9.15 years, duration of diabetes 3.9+/-3.07 years, BMI 26.2+/-3.26 kg/m2, waist circumference 97.7+/-9.88 cm and HbA1c 7.2+/-1.2%. Men and women were matched for age, duration of diabetes, BMI and HbA1c. The patients had a 330 kcal standard meal, blood samples were taken in fasting condition and 2 and 4 hours postprandial and the following parameters were obtained: glycemia, total cholesterol, HDL-cholesterol, triglycerides, apolipoprotein A1 and B and also CRP levels. The patients were also evaluated through duplex scan 2D ultrasound for intima-media thickness (IMT) of common carotid artery bilaterally. Data were analysed with Epi Info, SPSS and Statistica Software. RESULTS: Fasting CRP correlated to BMI and waist circumference (p=0.0068 and p=0.038 respectively). At two hours postprandial, we found a significant nonparametric correlation between CRP level and total cholesterol (p=0.01), which remained significant even after adjusting for age, BMI, HbA1c and blood pressure values (adjusted p=0.018). Patients in the lowest quartile for CRP level compared to those in the highest quartile had lower fasting apolipoprotein B levels (146 vs 197 mg/dl, p=0.042), lower postprandial blood glucose levels (188 vs 241 mg/dl, p=0.035) and lower nonHDL-cholesterol levels (148 vs 192 mg/dl, p=0.005). Common carotid artery IMT correlated with the duration of diabetes (p=0.026) and systolic blood pressure values both in clino and orthostatism (p=0.007 and p=0.006 respectively). CONCLUSION: The results confirm that C reactive protein and apolipoprotein B have close relationships with other components of the metabolic syndrome in type 2 diabetic patients. High CRP and apolipoprotein B levels could be a marker for an excessive postprandial response, leading to an increased risk for chronic vascular complications and atherogenesis.

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Diabetes mellitus is a complex disorder of the energy metabolism. In the present paper, we have tried to illustrate the changes in the regulation of blood glucose levels encountered in the two main types of diabetes: Type 2 (T2DM) and Type 1 (T1DM) diabetes mellitus, compared with healthy, non-diabetic subjects. For this we used the MiniMed CGMS (Continuous Glucose Monitoring System) which allows the continuous in vivo blood glucose measurement over a 3-day period. The study group comprised 19 diabetic patients (14 T1DM and 5 T2DM cases) and 4 non-diabetic controls. The recording in normal subjects showed a glycemic variation between 46 and 118 mg/dl, suggesting the existence of a strong and efficient glycemic control mechanism. In T2DM patients, both on diet only or on oral antidiabetic treatment, the oscillation of blood glucose levels was significantly higher compared to that recorded in non-diabetic subjects. In T1DM patients with stable metabolic control blood glucose fluctuations were comparable with those recorded in long-term type 2 diabetic patients but the "mean" values of blood glucose over 72 hours were lower. The CGMS is a valuable tool in the detection of unrecognized hypoglycemic episodes and hyperglycemic postprandial peaks and allows the patient and the health care team to adjust the treatment regimen in order to improve glycemic control. From our point of view, the CGMS could offer valuable information for the knowledge of glycemic regulation in normal people and for the diabetogenic mechanisms in prediabetic IGT and IFG patients.

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