Non-enzymatic glycation in diabetic complications.

D mellitus (DM) is associated with a greatly increased risk of secondary complications, such as cutaneous manifestations, myocardial infarction, nephropathy, retinopathy, and polyneuropathy. The non-enzymatic glycation of proteins followed by the formation of advanced glycation end products (AGEs) plays an important role in the pathology of diabetic complications.1 Occasionally endocrinological disorders, including DM, manifest themselves by their associated or induced cutaneous abnormalities. A little information is available on what common pathophysiologic theme is responsible for the skin manifestation in diabetes.2 Therefore, this study was carried out to investigate the extent of in vivo glycation of plasma proteins in type 2 diabetic patients with or without cutaneous manifestations. This study also demonstrated the outcome of treatments provided to the type 2 diabetic patients with skin manifestations. The study was carried out at the District Headquarter Hospital, Faisalabad, Pakistan, and Department of Chemistry and Biochemistry, Faculty of Sciences, University of Agriculture, Faisalabad, Pakistan, between November 2005 and March 2006. The Advanced Studies and Research Board (ASRB) of the University granted ethical approval for this study. Seventy-six patients of type 2 DM, and 40 healthy volunteers were recruited for the study after written informed consent. The patients under study were divided into 3 groups; group A consisted of 46 type 2 diabetic patients with skin manifestations, group B consisted of 30 type 2 diabetic patients without skin manifestations, and 40 healthy volunteers formed group C. The research period was divided into 2 phases: phase 1 (pre-treatment phase) and phase 2 (post-treatment phase) had 4 months interval. Different approaches adopted independently by physicians, patients, and caregivers to control type 2 diabetes and its complications were assumed as treatments. A certified dermatologist, nephrologists and retinal specialists carried out assessment of skin diseases, nephropathy, and retinopathy. The post-prandial blood sugar, total plasma proteins, and non-enzymatic plasma protein glycation levels were measured by laboratory kit (enzymatic method) and colorimetric techniques (Hitachi model U-2001 UV/VIS spectrophotometer, Hitachi, Japan). The data were analyzed using the statistical package for social sciences for Windows (version 12.0, 2003, ®SPSS Inc.) with significance level set at p≤0.01. The first group of 46 type 2 diabetics (22 women, 24 men) had a mean age of 59 ± 8.83 years (46.60 ± 5.38 years age at onset of diabetes). Among these, 23.9% had retinal complications, while 26.1% presented with kidney problem related to diabetes. Ichthyosiform (shins) (23.7%), scleroderma such as changes of the hands (sclerosis) (17%), diabetic foot ulcers (9%), dermatomycosis (6.6%) and tinea pedis (5.3%) were detected among these patients. The B group comprising 30 type 2 diabetic patients (12 women, 18 men) had a mean age of 54.4 ± 8.0 years (47.67 ± 5.43 years age at onset of diabetes). Retinal (20%) and kidney complications (16.6%) of diabetes were prevalent in those patients. In this study, 56% patients of group A had knowledge of diabetes as compared to 44% of group B. On the knowledge of related complications, equal prevalence (35%) was found for both A and B groups, whereas only 3% had knowledge on management. Statistical difference between the groups when analyzed for age at onset of diabetes was found non-significant (p=0.416). The mean post-prandial blood sugar of group A and B was initially 13.56 ± 3.16 mmol/L and 11.31 ± 2.39 mmol/L, and after 4 months the levels were 12.28 ± 3.02 mmol/L and 10.76 ± 2.03 mmol/L. Both the groups showed significant improvement (group A: p=0.000; group B: p=0.024) in post-prandial glucose levels however fall of post-prandial glucose at the end of the study was higher in group A, (-1.28 ± 0.14 mmol/L) than in group B (-0.55 ± 0.36 mmol/L). A significant reduction in total plasma proteins (p=0.000) was observed for group A that managed to reduce the mean levels from 14.53 ± 4.37 g/dl to 13.76 ± 4.20 g/dl. Group B showed increasing trend in total plasma proteins as mean value 12.08 ± 3.39 g/dl increased to 12.13 ± 2.97 g/dl. Final assessment after 16 weeks showed a significant difference (p=0.000) in mean levels of non-enzymatic plasma protein glycation (mole of glucose/mole of protein) for group A, from 1.66 ± 0.56 to 1.59 ± 0.52, as compared to slight increase in mean levels of non-enzymatic plasma protein glycation (mole of glucose/mole of protein) for group B, from 1.25 ± 0.56 to 1.29 ± 0.56 (normal range: post-prandial blood sugar = 140 mg/dl (7.77 mmol/L), total plasma protein = 6 g/dl, and non-enzymatic plasma proteins glycation = 0.4 mole glucose/mole protein). In the pre-treatment phase, group A showed a higher mean post-prandial Brief Communication