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Long-term Effects of Pioglitazone vs Glimepiride on Lipoproteins and Glyco-oxidation in Patients with Type 2 Diabetes
Full text linkBackground and aim
Cardiovascular complications are the first cause of mortality and morbidity in type 2 diabetic patients. Among antidiabetic drugs, those who have shown cardiovascular benefits have ancillary activities that simultaneously control several risk factors. In the PROACTIVE trial, pioglitazone determined a 16% reduction of death for all causes, non-fatal myocardial infarction, non-fatal stroke, compared to placebo. The aim of the study is to investigate the effects of 5 years treatment with pioglitazone/metformin compared to 5 years treatment with glimepiride/metformin on diabetic dyslipidemia, both quantitatively and qualitatively, and on glyco-oxidation processes.
Methods
96 diabetic patients, treated with metformin (2g/day) for at least 2 months, were randomized to treatment with pioglitazone or glimepiride. Patients were followed for 5 years: body mass index (BMI), waist circumference (CV), blood pressure, HbA1c; total cholesterol (CT), high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides (TG), advanced glycation end products (AGE), oxidized LDL (oxLDL) were determined at baseline and after 5 years of treatment.
Results
Treatment with pioglitazone resulted in significant increase in HDL (47.1±11.7 vs 51.3±15.7 mg/dl; p=0.02), non-significant reduction in CT, LDL and TG. Glimepiride treatment resulted in a significant reduction in HDL (48.6±14.1 vs 45.8±12.7 mg/dl; p=0.03), a non-significant reduction in CT, LDL and TG. Only the variation of HDL and oxLDL were significantly different between the two groups (ΔHDLPioglitazone= +4.2±10.5 mg/dl vs ΔHDLGlimepride= -2.9±7.7 mg/dl; p=0.002); (ΔoxLDLPioglitazone= -2.1±9.8 U/l vs ΔoxLDLGlimepride= +3.6±11.4 U/l; p=0.01).
AGEs reduction, significant for both treatments, is not significantly different between the two groups. HbA1c reduction was significant only in patients treated with glimepiride (7.7±0.4 vs 7.1±0.8 %; p <0001) and was not correlated with AGEs variation (r=1.22; p=0.59).
Conclusions
Long-term treatment with pioglitazone significantly improves lipid profile of type 2 diabetic patients, increasing HDL levels and reducing oxLDL levels. In addition, it reduces AGEs formations. The inhibition of glyco-oxidative processes is one of the mechanisms that may explain the drug ability to prevent cardiovascular events
AGEs, rather than hyperglycemia, are responsible for microvascular complications in diabetes: a "glycoxidation-centric" point of view.
No full textAIMS:
Advanced glycation end products (AGE) excess is one of the most important mechanisms involved in the pathophysiology of chronic diabetic complications. This review first summarizes the role of these compounds in microvascular pathogenesis, particularly in the light of recently proposed biochemical mechanisms for diabetic retinopathy, nephropathy and neuropathy. Then we focus on the relationship between AGE and metabolic memory, trying to clarify the former's role in the missing link between micro- and macrovascular complications.
DATA SYNTHESIS:
An excessive AGE formation has been demonstrated in the newly disclosed biochemical pathways involved in the microvascular pathobiology of type 2 diabetes, confirming the central role of AGE in the progression of diabetic neuropathy, retinopathy and nephropathy. As shown by recent studies, AGE seem to be not "actors", but "directors" of processes conducting to these complications, for at least two main reasons: first, AGE have several intra- and extracellular targets, so they can be seen as a "bridge" between intracellular and extracellular damage; secondly, whatever the level of hyperglycemia, AGE-related intracellular glycation of the mitochondrial respiratory chain proteins has been found to produce more reactive oxygen species, triggering a vicious cycle that amplifies AGE formation. This may help to explain the clinical link between micro- and macrovascular disease in diabetes, contributing to clarify the mechanisms behind metabolic memory.
CONCLUSIONS:
The pathophysiological cascades triggered by AGE have a dominant, hyperglycemia-independent role in the onset of the microvascular complications of diabetes. An effective approach to prevention and treatment must therefore focus not only on early glycemic control, but also on reducing factors related to oxidative stress, and the dietary intake of exogenous AGE in particular
Weight gain during pregnancy: A narrative review on the recent evidences
No full textGestational weight gain is necessary for the normal fetus development, in fact a series of studies have evidenced that both low and excessive gestational weight gain is associated with negative fetal-neonatal outcomes. So, evidences on the optimal gestational weight gain across the ranges of the pre-pregnancy maternal body mass index are necessary. In this context, while for normal weight and underweight the recommendations of IOM are clearly stated and supported by well designed and conducted clinical studies, those for the obese pregnant women are even today debated. Pre-pregnancy obesity is associated with high risk to develop hypertension, gestational diabetes, cesarean section and high birth weight. The Institute of Medicine guidelines, in 2009, recommended that women with obesity gain 11-20 lb at a rate of 0.5 lb/week during the second and third trimesters of pregnancy. Successively, taking into account a series of meta-analysis, the American College of Obstetricians and Gynecologists emphasized that the IOM weight gain targets for obese pregnant women are too high. However the high risk to have babies small for gestational age, related to a low weight gain or a losing of weight during pregnancy, has also been demonstrated. More recent studies have taken into consideration the maternal and fetal outcomes of obese pregnant women with different obesity class (I,II,III) and different weight gain during pregnancy. The analysis of these studies, discussed in this narrative review, show that the appropriate gestational weight gain should be personalized considering the three obesity class; furthermore both an upper and lower limit of gestational weight gain should be reconsidered in order to prevent the negative maternal and fetal outcomes in these women
Between reduction of glucose fluctuations and increased therapeutic adherence: an example of the benefits of vildagliptin in an elderly diabetic patient.
No full textA case report on use of dulaglutide during the first weeks of pregnancy in woman affected by type 2 diabetes mellitus
No full textAssociation between glucose variability as assessed by continuous glucose monitoring (CGM) and diabetic retinopathy in type 1 and type 2 diabetes.
No full textPregnancy and Type 2 Diabetes: Unmet Goals
Full text linkThe increased frequency of type 2 diabetes worldwide has led to a concomitant increase in pregnancies complicated by type 2 diabetes for the past 20 years. This is mainly due to two factors: the earlier age of diabetes onset and the advanced age of pregnancy occurrence. Patients with type 2 diabetes in pregnancy show a high frequency of maternal and fetal complications, posing a series of problems in the follow-up of these women. In this narrative review, changes in epidemiology, maternal and fetal complications, and evidence of critical unmet needs before and during pregnancy complicated by type 2 diabetes are reported and discussed to review the possible approaches
Pregnancy after Bariatric Surgery: Nutrition Recommendations and Glucose Homeostasis: A Point of View on Unresolved Questions
Full text linkObesity is increasing in all age groups and, consequently, its incidence has also risen in women of childbearing age. In Europe, the prevalence of maternal obesity varies from 7 to 25%. Maternal obesity is associated with short- and long-term adverse outcomes for both mother and child, and it is necessary to reduce weight before gestation to improve maternal and fetal outcomes. Bariatric surgery is an important treatment option for people with severe obesity. The number of surgeries performed is increasing worldwide, even in women of reproductive age, because improving fertility is a motivating factor. Nutritional intake after bariatric surgery is dependent on type of surgery, presence of symptoms, such as pain and nausea, and complications. There is also a risk of malnutrition after bariatric surgery. In particular, during pregnancy following bariatric surgery, there is a risk of protein and calorie malnutrition and micronutrient deficiencies due to increased maternal and fetal demand and possibly due to reduction of food intake (nausea, vomiting). As such, it is necessary to monitor and manage nutrition in pregnancy following bariatric surgery with a multidisciplinary team to avoid any deficiencies in each trimester and to ensure the well-being of the mother and fetus
Gestational Diabetes Mellitus and Future Cardiovascular Risk: An Update
Full text linkThe prevalence of gestational diabetes mellitus is increasing in parallel with the rising prevalence of type 2 diabetes and obesity around the world. Current evidence strongly suggests that women who have had gestational diabetes mellitus are at greater risk of cardiovascular disease later in life. Given the growing prevalence of gestational diabetes mellitus, it is important to identify appropriate reliable markers of cardiovascular disease and specific treatment strategies capable of containing obesity, diabetes, and metabolic syndrome in order to reduce the burden of cardiovascular disease in the women affected
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