Ma. Eugenia Garay-Sevilla

Adherence to treatment and social support in patients with non-insulin dependent diabetes mellitus

We carried out a cross-sectional study to investigate factors associated with adherence to diet and medication in non-insulin-dependent diabetes mellitus (NIDDM) patients. A total of 200 patients not seeking treatment from clubs for diabetics from two hospitals in León, Mexico, accepted inclusion. Patients interviewed had a mean age of 58.8 (53.3-56.4, 95% C.I.) years. We evaluated adherence to diet and medication, knowledge on diabetes, social support, familys structure and functioning (with a modified McMaster model), metabolic control, and complications. Stepwise multiple regression procedure showed that adherence to diet was associated with years since diagnosis (p = 0.003) and with social support (p = 0.007). Adherence to medication was associated with social support (p = 0.002), and the age of the spouse (p = 0.016). Adherence to medication was lower in patients from families with rigid control than in the group with Laissez-faire type of control (p = 0.010) or the group with flexible control (p = 0.002). Social support was lower in the group with chaotic control than that in the group with flexible control (p < 0.001). Compliance to diet was associated with peripheral neuropathy and plasma creatinine, and adherence to medication with plasma glucose and peripheral neuropathy. We concluded that (1) adherence to treatment in NIDDM patients is associated with social support; (2) some aspects related to the family, such as the age of the spouse and the control of behavior, were also associated with compliance to treatment; and (3) it is important for the practicing physicians, and for institutional programs, to consider factors associated with adherence to treatment.

Dietary Advanced Glycation End Products and Their Role in Health and Disease

Over the past 2 decades there has been increasing evidence supporting an important contribution from food-derived advanced glycation end products (AGEs) to the body pool of AGEs and therefore increased oxidative stress and inflammation, processes that play a major role in the causation of chronic diseases. A 3-d symposium (1st Latin American Symposium of AGEs) to discuss this subject took place in Guanajuato, Mexico, on 1-3 October 2014 with the participation of researchers from several countries. This review is a summary of the different presentations and subjects discussed, and it is divided into 4 sections. The first section deals with current general knowledge about AGEs. The second section dwells on mechanisms of action of AGEs, with special emphasis on the receptor for advanced glycation end products and the potential role of AGEs in neurodegenerative diseases. The third section discusses different approaches to decrease the AGE burden. The last section discusses current methodologic problems with measurement of AGEs in different samples. The subject under discussion is complex and extensive and cannot be completely covered in a short review. Therefore, some areas of interest have been left out because of space. However, we hope this review illustrates currently known facts about dietary AGEs as well as pointing out areas that require further research.

Serum selenium and glutathione peroxidase concentrations in type 2 diabetes mellitus patients

AIMS Antioxidant selenium (Se) properties and, its protective role against oxidative damage play an important role in diabetic complications. Our objective was to gain further insight on a link between selenium status and diabetic nephropathy. METHODS We assessed glutathione peroxidase (GPx) and Se in type 2 diabetes mellitus patients with microalbuminuria (MA) (group 1), without microalbuminuria (group 2), and in control subjects (group 3). Glucose, urea, creatinine and glycated hemoglobin tests were tested in sera. A complete clinical record was elaborated. RESULTS For diabetic patients both, the time from diagnosis and plasma glucose concentration were higher in group 1 as compared to group 2. Control group showed higher serum Se concentrations as compared to the diabetic groups. The two groups of diabetic patients showed similar serum Se levels. Serum concentration of GPx was significantly lower in group 1 as compared to groups 2 and 3. Microalbuminuria (MA) test showed a positive correlation with glucose, and a negative relationship with serum Se and GPx. Multiple regression revealed an inverse relationship between selenium or GPx in serum and the results of the MA test. CONCLUSIONS Our results suggest that lower Se and GPx levels in diabetic patients may be implicated in the diabetic nephropathy.

Telomere length and type 2 diabetes in males, a premature aging syndrome

Background: Increased telomere shortening has been demonstrated in several diseases including type 2 diabetes. However, it is not known whether telomere length changes during the course of type 2 diabetes. Objective: To determine telomere length at different stages of type 2 diabetes, including early and late stages. Methods: A total of 93 males with type 2 diabetes and 10 years or more since original diagnosis; 96 males with less than one year of diagnosis; 98 age matched healthy males. Telomere length was estimated by means of real-time polymerase chain reaction. Fasting venous blood samples were obtained for measurement of lipid peroxidation and inflammation markers.Results: We found a greater telomere shortening in group (A) with type 2 diabetes of 10 years or more since original diagnosis, compared with the control group (C) of healthy males (5.4 vs 9.6 Kb) (p = 0.04) and with group B (5.4 vs 8.7kb) (p = 0.05). With regard to inflammatory markers TNF-α, malondialdehyde peroxidation and adiponectin we found significant differences. Conclusion: Telomere shortening increases with the duration of diabetes. The time of exhibition suggests in parallel that the progressive increase of inflammation and/or oxidative stress plays a direct role in telomere shortening.

Advanced glycosylation end products in skin, serum, saliva and urine and its association with complications of patients with Type 2 diabetes mellitus

Background: The accumulation of advanced glycation end products (AGEs) has a key role in the pathophysiology of diabetes complications. Comparison of AGEs measurement in serum, skin, saliva and urine has not been reported. Aims: To compare AGEs in serum, skin, saliva and urine in patients with Type 2 diabetes mellitus, with complications at different stages. Materials and Methods: We examined 50 patients with Type 2 diabetes mellitus (40 women and 10 men) grouped according to the progression of neuropathy, nephropathy and retinopathy. The AGEs content in serum, skin, saliva and urine was measured by spectrofluorometry HPLC. Results: The patients had a mean age of 56.5±7.7 yr and 12.8±6.7 yr since diagnosis. AGEs in skin correlated with years since diagnosis (p=0.0005). AGEs in serum, skin and saliva increased with the progression of complications, nevertheless, in urine a trend to diminution was found. In the group with end-stage renal disease (ESRD), AGEs in serum increased in greater proportion. In order to account for the decreased AGEs clearance, we corrected the values for creatinine levels, and AGEs in skin gave a better association with complications. Conclusions: The AGEs measurement in skin, serum and saliva are useful to evaluate diabetes complications. AGEs in skin are associated with years since diagnosis of diabetes. Correction for renal function might discriminate AGEs in situ formation from accumulation.

Advanced glycosylation end products (AGEs), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) in patients with Type 2 diabetes mellitus

Advanced glycosylation end product (AGE) formation is a major mechanism for the development of complications in diabetes, and the possible roles of insulin‐like growth factor 1 (IGF‐1) and IGF binding protein 3 (IGFBP‐3) are not clearly established.

Effect of an advanced glycation end product-restricted diet and exercise on metabolic parameters in adult overweight men

OBJECTIVES The aim of this study was to review the effect of a low advanced glycation end product (AGEs) diet, exercise, and a combination of both on circulating AGE levels as well as on plasma lipids and anthropometric parameters. METHODS Forty-three overweight or obese men (body mass index [BMI] >25 kg/m(2)), 30 to 55 y, participated in a 12-wk study and were randomly assigned to one of three groups: low AGE diet, exercise with habitual food intake, or exercise plus low AGE diet. Exercise was for 45 min at 65% to 75% of their maximum heart rate three times a week. We measured somatometric variables (BMI and waist circumference), blood glucose, lipids, and serum AGEs (N(ε)-[Carboxymethyl]Lysine [CML] and methylglyoxal [MG]) at baseline and at 12 wk. RESULTS Exercise alone was associated with decreased somatometric variables; the low AGE diet had the same effects and decreased serum CML and MG and when combined with exercise reproduced all these effects, but also decreased triacylglycerols and increased high-density lipoprotein. Correlation analysis showed that both changes of CML and MG correlated with changes in dietary AGEs (P < 0.020 and P < 0.038, respectively); change in maximum oxygen consumption correlated inversely with change in weight and triacylglycerols. Regression analyses, including change in dietary AGEs and in dietary calories, showed that change in dietary AGEs was the independent determinant of change in CML (P < 0.020) and MG (P < 0.038). CONCLUSIONS An AGE-restricted diet reduces serum AGE and indices of body fat. The addition of exercise to the restricted diet has the same effects but also improves lipid profile.

Association of the TNF-α -308G/A polymorphism with family history of type 2 diabetes mellitus in a Mexican population.

AIMS We examined the possible association of the -308G/A polymorphism of the TNF-α promoter gene in type 2 diabetes mellitus (DM2) patients and in non-diabetic subjects with and without family history of DM2. METHODS We studied 87 non-diabetic subjects without DM2 family history in at least one of two generations, 48 non-diabetic subjects with DM2 family history and 95 DM2 patients. Genotyping was carried out by PCR-RFLP. RESULTS The frequency of TNF-α -308G/A genotype was significantly lower in non-diabetic subjects without DM2 relatives (6%) as compared to DM2 patients (24%) (odds ratio (OR)=5.24; 95% confidence interval (CI)=1.9-15.8, p<0.0005), but similar to non-diabetic subjects with DM2 relatives (29%) (OR=0.77; CI=0.3-1.7, p=0.4). Logistic regression analysis showed the association of TNF-α -308G/A polymorphism with DM2 family history (OR=5.80; CI=1.77-18.98, p<0.0003). CONCLUSIONS Our results suggest that TNF-α -308G/A polymorphism is associated with DM2 family history and is a risk factor for DM2.

High-performance liquid chromatography determination of glyoxal, methylglyoxal, and diacetyl in urine using 4-methoxy-o-phenylenediamine as derivatizing reagent.

Bioanalytical relevance of glyoxal (Go) and methylglyoxal (MGo) arises from their role as biomarkers of glycation processes and oxidative stress. The third compound of interest in this work is diacetyl (DMGo), a component of different food products and alcoholic beverages and one of the small α-ketoaldehydes previously reported in urine. The original idea for the determination of the above compounds by reversed phase high-performance liquid chromatography (HPLC) with fluorimetric detection was to use 4-methoxy-o-phenylenediamine (4MPD) as a derivatizing reagent and diethylglyoxal (DEGo) as internal standard. Acetonitrile was added to urine for matrix precipitation, and derivatization reaction was carried out in the diluted supernatant at neutral pH (40 °C, 4 h); after acidification, salt-induced phase separation enabled recovery of the obtained quinoxalines in the acetonitrile layer. The separation was achieved within 12 min using a C18 Kinetex column and gradient elution. The calibration detection limits for Go, MGo, and DMGo were 0.46, 0.39, and 0.28 μg/L, respectively. Within-day precision for real-world samples did not exceed 6%. Several urine samples from healthy volunteers, diabetic subjects, and juvenile swimmers were analyzed. The sensitivity of the procedure proposed here enabled detection of differences between analyte concentrations in urine from patients at different clinical or exposure-related conditions.

Determination of putrescine, cadaverine, spermidine and spermine in different chemical matrices by high performance liquid chromatography–electrospray ionization–ion trap tandem mass spectrometry (HPLC–ESI–ITMS/MS)

The goal of this work was to establish a simple HPLC-ESI-ITMS/MS procedure, suitable for the determination of four common aliphatic polyamines in two different types of biological matrices. To this end, 1,6-diaminohexane was used as the internal standard (IS) and 4-fluoro-3-nitrobenzenotrifluoride (FNBT) as the derivatizing agent. Formation of fully derivatized compounds was confirmed by high resolution ESI-QTOFMS and MS/MS analysis. Reversed phase chromatographic separation was carried out by gradient elution with 0.1% (v/v) formic acid and methanol. In a positive ESI mode, the following pairs of precursor/quantifier ions were used for multiple reaction monitoring: 467.4/261.0 for PUT, 481.2/461.1 for CAD, 713.7/261.0 for SPD, 959.8/507.2 for SPM and 495.3/475.2 for IS. On-column instrumental detection limits of four polyamines were in the range 0.62-2.14fmol (0.039-0.215ng/ml). Versatility was demonstrated by analyzing plant extracts and human urine; prior to derivatization, all samples were cleaned-up by dichloromethane extraction. The evaluated signal suppression/enhancement was in the range 82.3-115.4% and the percentage recoveries obtained in the method of standard addition were in the range 83.7-114.4%. Statistically significant differences in polyamines concentrations were found in garden cress exposed to Cd(II) versus control seedlings (t-test, p<0.05); results obtained for urine from healthy volunteers and diabetic patients at different clinical conditions suggested possible utility of free polyamines as biomarkers of progressive diabetes.