Several important developments in the diagnosis and treatment of diabetes mellitus occurred during the last year. First of all, continuing its initiative from 2010, in January 2011, the American Association of Diabetes (ADA) included in its annual clinical practice guideline the use of glycated haemoglobin (HbA1c) as a diagnostic criterion for diabetes mellitus (1). Thus, HbA1c ≥6.5% is diagnostic for diabetes. HbA1c between 5.7%-6.4% is considered to define one of the categories of increased risk for diabetes (prediabetes): IFG and IGT, while a HbA1c < 5.7% is considered to be normal. In order to be valid, the diagnostic test should be performed using a method that is standardized or traceable to the Diabetes Control and Complications Trial (DCCT) reference assay. The use of HbA1cwas proposed also by the EASD (European Association for the Study of Diabetes) but it is up to the national diabetes associations to include it in their local clinical practice guidelines.
In respect to the current clinical practice, following the results of the major trials of cardiovascular prevention in type 2 diabetes (ACCORD, ADVANCE, VADT an UKPDS 10 year follow up analysis), it was established that intensive glycemic control leads to a decrease of the microvascular diabetic complications but it does not decrease the frequency of cardiovascular events, at least not during the active period of the trial (2). The positive effect becomes however evident after 10 years of follow-up (metabolic memory effect), highlighting the importance of a tight glycemic control at the diagnosis of T2DM (2). The practical conclusion is that therapeutic targets in T2DM should be individualized to each patient. Thus, in older and more vulnerable patients, with concomitant CVD and limited life expectancy, who don't tolerate hypoglycaemia the HbA1c target should be ≈7.5%-8%. Contrariwise, in younger patients without CVD, a HbA1c < 7% should be targeted, even <6.5% if this can be achieved without hypoglycaemia.
There were a number of reports and reviews about diabetes and cancer. The key take-home message of the last 12 months is that T2DM patients are at increased risk for cancer and they should be periodically screened for specific malignancies. On the positive side, metformin was reconfirmed to reduce the risk of cancer in T2DM and may also reduce mortality (3). This strengthens the position of metformin as the first step in the treatment of T2DM.
Another major topic was represented by drugs used for T2DM treatment. The last year brought the dawn of Thiazolidindiones. Thus, on 23 September 2010, EMEA recommended a ban on drugs containing Rosiglitazone (Avandia, Avandamet and Avaglim). In the same time, the FDA restricted drastically its use in the USA – it cannot be prescribed as a first line drug but only when other therapies failed. The main reason was the increasing evidence confirming the initial report of Niessen from 2007 regarding an increased risk of MI in patients using Rosiglitazone. In addition, the RECORD study (sponsored by GlaxoSmithKline) failed to show any benefit of this drug in CVD prevention (4). Also during the last year, data was published (5) regarding the increased risk of bladder cancer in T2DM patients treated with Pioglitazone (Actos). The risk is higher in those patients exposed to the highest cumulative doses of Pioglitazone, especially the elderly. Following these reports France and Germany suspended the use of Pioglitazone while the FDA recommended a labelling update for Pioglitazone regarding this risk. A single European position regarding this issue is still waited from EMEA.
The hopes for the launch of a new class of oral antidiabetic drugs – inhibitors of the sodium glucose cotransporter-2 (SGLT-2) in the proximal renal tubules were also set back. Thus, in July 2011, the FDA voted against the approval of dapagliflozin (Bristol-Myers Squibb and AstraZeneca), largely because of fears that the product may cause breast and bladder cancer. Additional concern was related to the lack of absence of hard pharmacokinetic data regarding this drug.
To finish on a brighter side this up-to-date in diabetology, two new drugs from the class of GLP-1 receptor agonists were approved for clinical practice last year. These are Liraglutide (Victoza from Novo Nordisk) that was approved by the FDA for use in the USA (it was already used in Europe for a couple of years) and the once-weekly exenatide (Bydureon from Eli Lilly and Amylin Pharmaceuticals) that was approved by EMEA for use in the UE.
Background and aims. Increased fat accumulation associated to increased cardiometabolic risk factors is a prominent feature of type 2 diabetes. In type 1 diabetes, increased fat accumulation is not prevalent and its metabolic impact has not been fully evaluated. We aimed to evaluate differences in body composition, clinical and metabolic profile in type 1 and type 2 diabetes patients with varying degrees of adiposity. Materials and methods. Clinical, biochemical and body composition data (using a bioelectric impedance analyzer) from 96 type 1 and 253 type 2 adult diabetes patients have been collected. Results. In type 1 patients estimated visceral fat area (eVFA) increased significantly (84.3±27.9 vs. 103.0±27.9 vs. 128.1±29.1 cm 2 , p=0.006, 0.003, and 25 kg/m 2 ) type 1 patients there were no significant differences either in triglycerides (128.7±135.6 vs. 92.8±50.6 mg/dl, p=0.1), HDL-cholesterol (53.6±15.9 vs. 52.3±13.7 mg/dl, p=0.6) and uric acid levels (3.4±2.0 vs. 2.9±1.2 mg/dl, p=0.2), or in hypertension (39.5% vs. 40.0%, p=0.7) and nonalcoholic hepatosteatosis (NASH) (10.0% vs. 10.5%, p=0.6) prevalences. In type 2 patients, BMI (32.3±5.9 vs. 29.5±5.1 vs. 27.9±5.0 kg/m 2 , p=0.001, p=0.04, p<0.001) and BFM (34.5±12.7 vs. 29.6±10.2 vs. 27.1±10.8 kg, p=0.007, p=0.11, p <0.001) decreased, while eVFA did not differ across age tertiles, suggesting that older age increases central fat distribution. Compared to normal weight, overweight type 2 diabetes patients had greater triglycerides (218.8±303.4 vs. 110.9±44.9 mg/dl, p=0.01), uric acid (4.5±2.4 vs. 3.3±1.4 mg/dl, p=0.01), and lower HDL-cholesterol (43.9±12.9 vs. 54.1±15.4 mg/dl, p<0.001) serum levels, and higher prevalences of hypertension (71.8% vs. 39.4%, p=0.005) and NASH (59.1% vs. 25.0%, p=0.005). Conclusion. Visceral fat accumulation is associated with older age in both types of diabetes, but only in type 2 diabetes is associated with cardiometabolic anomalies.
Objective: Athlete's heart is associated with left ventricular (LV) hypertrophy (LVH), and “supranormal” cardiac function, suggesting that this is a physiological process. Hypertrophy alone cannot explain increase in cardiac function, therefore, other mechanisms, such as better ventriculo‐arterial coupling might be involved. Methods: We studied 60 male (21 ± 3 years) subjects: 27 endurance athletes, and a control group of 33 age‐matched sedentary subjects. We assessed global systolic and diastolic LV function, short‐ and long‐axis myocardial velocities, arterial structure and function and ventriculo‐arterial coupling, endothelial function by flow‐mediated dilatation, and amino‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and biological markers of myocardial fibrosis and of oxidative stress. Results: Athletes had “supranormal” LV longitudinal function (12.4 ± 1.0 vs 10.1 ± 1.4 cm/s for longitudinal systolic velocity, and 17.4 ± 2.6 vs 15.1 ± 2.4 cm/s for longitudinal early diastolic velocity, both P < 0.01), whereas ejection fraction and short‐axis function were similar to controls. Meanwhile, they had better endothelial function (16.7 ± 7.0 vs 13.3 ± 5.3%, P < 0.05) and lower arterial stiffness (pulse wave velocity 7.1 ± 0.6 vs 8.8 ± 1.1 m/s, P = 0.0001), related to lower oxidative stress (0.259 ± 0.71 vs 0.428 ± 0.88 nmol/mL, P = 0.0001), with improved ventriculo‐arterial coupling (37.1 ± 21.5 vs 15.5 ± 13.4 mmHg.m/s 3 × 10 3 , P = 0.0001). NT‐proBNP and markers of myocardial fibrosis were not different from controls. LV longitudinal function was directly related to ventriculo‐arterial coupling, and inversely related to arterial stiffness and to oxidative stress. Conclusions: “Supranormal” cardiac function in athletes is due to better endothelial and arterial function, related to lower oxidative stress, with optimized ventriculo‐arterial coupling; athlete's heart is purely a physiological phenomenon, associated with “supranormal” cardiac function, and there are no markers of myocardial fibrosis. (Echocardiography 2010;27:659‐667)
The genetic characteristics of the diabetic types have been assessed by following up their frequency in first degree relatives of some non-selected diabetic patients, registered at eight different centers of the country. Out of 1,003 non-diabetic controls only 46 (4.6%) had 52 diabetic relatives, 65.4% of type 2 (non-insulin-dependent). Comparatively, out of the 704 patients, 172 (24.4%) had 229 diabetic first degree relatives, 72.5 of type 2. Out of 231 type 1 (insulin-dependent) diabetic patients, 29 (12.6%) had 34 diabetic relatives, 55.9% of type 1. Out of 300 type 2 patients, 99 (33.0%) had 121 diabetic relatives, 84.0% of type 2. The other 173 diabetic patients presented an "intermediary" type of the disease (needing insulin many years after onset). Forty-four (25.4%) of them had 64 diabetic relatives, 67.2% of type 2, 20.3% of type 1 and 12.5% with "intermediary" diabetes. The five times higher frequency of diabetes in patients' relatives versus controls is pointed out. Type 2 diabetic relatives predominated. The proportion of probands with diabetic relatives increased from 4.6% in non-diabetics to 12.6% in type 1, to 25.4% in "intermediary" diabetes and to 33.0% in type 2. The heredity of type 1 prevailed in type 1 and that of type 2 in type 2 and in "intermediary" diabetes. The fact that "intermediary" diabetes tends towards type 1 (insulin-dependent) as therapy and towards type 2 (non-insulin-dependent) as heredity might be an argument supporting the controversy on the diabetic syndrome classification.
Abstract The objective of this position paper is to review the current medical evidence and guidelines regarding the treatment of type 2 diabetes (T2DM) and to issue medical recommendations strengthening the timely use of insulin in patients with T2DM uncontrolled on noninsulin therapy. When noninsulin therapy fails to achieve or to maintain HbA1c targets, insulin therapy is required. Timely insulin therapy could provide proper metabolic control that might prevent complications, lead to improvement of life expectancy and quality of life.
Background: The impact of smoking on morbidity is well known, but in Romania, limited data are available regarding the smoking prevalence and relationship with cardiometabolic profile and kidney function.Objectives: To assess the association of smoking with cardiometabolic traits and kidney function, in a Romanian population-based sample from the PREDATORR study.Methods: PREDATORR was an epidemiological cross-sectional study. Between 2012 and 2014, participants were randomly selected from the lists of general practitioners and enrolled if they were aged 20 to 79 years, born and living in the past 10 years in Romania. Sociodemographic and lifestyle characteristics were collected through interviewer-administered questionnaires.Results: Overall, 2704 participants were included in the analysis, 18% of them being current smokers and 30.8% former smokers. Current smokers compared to non-smokers had higher total cholesterol (220.6 ± 50.4 versus 213.9 ± 86.8 mg/dl, P = 0.017), LDL-cholesterol (137.8 ± 45.2 versus 130.7 ± 83.7 mg/dl, P = 0.004) and glomerular filtration rate (96.9 ± 16.8 versus 90.7 ± 19.1 ml/min/1.73 m2, P <0.001) in women and higher triglycerides (170.7 ± 129.8 versus 144.3 ± 94.2 mg/dl, P = 0.007), glomerular filtration rate (97.6 ± 17 versus 90.3 ± 18 ml/min/1.73 m2, P < 0.001) and lower HDL-cholesterol (48 ± 15.5 versus 50.4 ± 14.1 mg/dl, P = 0.002) in men. Active smoking was associated with hypercholesterolaemia [OR: 1.40 (95% CI: 1.01–1.96), P = 0.04] and low HDL-cholesterolaemia [OR: 1.39 (95% CI: 1.01–1.91), P = 0.04] and negatively associated with overweight/obesity [OR: 0.67 (95% CI: 0.48–0.94), P = 0.02]. Male former smokers had higher prevalence of abdominal obesity (82.4% versus 76.4%, P = 0.02), hypertriglyceridaemia (43.6% versus 35.6%, P = 0.01), hypertension (64% versus 56.4%, P = 0.01) and ischaemic vascular disease (40.5% versus 30.9%, P = 0.003) than male non-smokers.Conclusion: The PREDATORR study showed a high prevalence of smoking in the adult Romanian population providing data on the association of smoking with cardiometabolic traits.
Glucose tolerance (75 g OGTT, according WHO) during the third trimester of pregnancy, in 302 women, has formerly been evaluated. Of these, 37 women were reinvestigated, with the same methodology, in absence of pregnancy and lactation, 2 years postpartum. According to oral glucose tolerance three groups were differentiated: group A (n = 14) with normal glucose tolerance (NGT) both in pregnancy and postpartum. Group B1 (n = 12) with impaired glucose tolerance (IGT) in pregnancy but NGT postpartum. Group B2 (n = 11) with IGT both in pregnancy and postpartum. B2 group had increased values (mean + SD) for age (37.0 +/- 6.6 years) versus B1 (30.2 +/- 5.5; p < 0.02) and A (29.5 +/- 5.9); p < 0.02) groups and BMI (32.5 +/- 4.2) versus 26.4 +/- 5.2; p < 0.01 and 23.3 +/- 4.4; p < 0.001 respectively). The ratio between basal insulinogenic indexes (microU IRI/mg BG) during pregnancy and 2 years postpartum has been significantly reduced in B1 (1.4 +/- 0.8) and B2 (1.5 +/- 0.6) as compared to A (2.5 +/- 1.1; p < 0.01) group suggesting, by comparison, the persistence of an increased level of insulin resistance postpartum in B1 and B2 groups. Insulinogenic index, after oral glucose was lower in B2 (34.4 +/- +/- 7.8) versus B1 (53.5 +/- 20.9; p < 0.01) group. These results suggest that, on an increased insulin resistance background, the decrease in glucose induced insulin response and increase in age and BMI are associated to deterioration of glucose tolerance early in the natural history of NIDDM.
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