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Table of Content - Volume 3 Issue 1 - July 2017
Study of protein metabolism associated with diabetes mellitus
Kamalakar Mane1*, Shilpa Asegaonkar2, Arvind Gaikwad3, Mahendra Kamble4
1,4Assistant Professor, 2,3Associate Professor, Department of Biochemistry, Government Medical College and Cancer Hospital, Aurangabad, Maharashtra, INDIA. Email: drkamlakarmane@gmail.com
Abstract Background: Diabetes mellitus (DM) is ametabolic disease affecting mainly carbohydrate metabolismcon sequenttothis, lipid and protein metabolism area is affected. It is proposed that DM which is due to insulin deficiency affects protein metabolism by increasing the circulating amino acids due to decrease dup take of amino acids by the tissues. The study intends to understand the role of proteins and serum enzymes in patients of DM. Methods: Present study involved 100 participants of which 50 were fresh lydetected diabetic patients and 50 were age and ex-matched healthy controls that fulfilled inclusion criteria. Blood samples were drawn under as eptic precaution from cases of DM and healthy controls. Necessary investigations were carried out and values were tabulated for cases and controls separately for statistical evaluation. Results: Serum amino acid levels increased significantly (p<0.001) from 8.12 (baseline) to 12.23. Glycated hemoglobin levels increased significantly (p<0.001) from5.12 (baseline) to11.03. Total proteins levels slight decreased (P<0.327) from 7.52 to 5.26. Albumin levels decreased (P<0.039) from 4012 to 4.69 Globulin level increased (P<0.721) from 1.44 (baseline) to 1.89. A/Gratio levels decreased (P<.631) from 2.09 (baseline) to 1.98. AST levels decreased (p<0.791) from 22.17 (baseline) to 20.32 and ALT levels was also decreased (P<0.627) from 24.29 (baseline) to 21.63 which showed small effect. Conclusion: Freshly detected Diabetic patients were associate statistically significant increase in circulating amino acids which is proportion alto percentage of Glycated hemoglobin and other parameters like Total protein, Albumin, A/Gratio, serumenzymes AST, and ALT levels showed statistically significant decreased levels. The mechanism and clinical significance of these finding are currently unknown and warrant further study. Key Words: Diabetes mellitus, Aminoacids, Glycated hemoglobin, Amino acid Pool.
INTRODUCTION Diabetes mellitus (DM) is the most common endocrinal disease in the world today. It is a major health care problem, not only in developed nations, but also in the developing nations like India. Indeed amongst the various ethnic groups, Asian Indian as seems to be at a particularly greaterriskofdevelopingdiabetes1 WHO estimated doubling of the total number of patients between 1994 and 2010. In round figures the total number in the world is to rise from110 to 230 millions. While in India the estimate rise likely to be from 17.5 to 47.0 millions2 In India at present there are 4 to 5 crore diabetics. At the end of 2004, 28.1% elderly of >60years has DM3. In rural South India 13.4% of people are supposed to have DM4 Concomitant with the increasing prevalence of DM, the prevalence of micro and macrovascular accidents, peripheral vascular disease like retinopathy, neuropathy, nephropathy and other complications are likely occur in the most productive years of life causing severe economic and social burden4 Diabetes mellitus is a degenerating disease mainly affecting carbohydrate metabolism. Consequent to this, metabolism flipids and proteins are also affected. In case of lipids, the derangementis limited to ketosis and ketoacidosis. In case of protein metabolism, the effect is wide spread and affects all functions of the body. Insulin is a nanabolichormone; its deficiency affects overall protein biosynthesis. This aspect is reflected by changes in circulating amino acid pool and also keyenzymes of protein metabolism namely As partateamino transferees (AST) with E.C. and Alanmine aminotransferase (ALT) with E.C. 2.6.1.2. Ageing which is a natural degenerative process also affects protein metabolism. Age in associated with diabetes mellitus will lead to increased change sinmetabolism of proteins. Hence it is proposed to study age dependent changes in aminoacidpool, serumproteins, glycated protein and transaminases. This will be correlated with changes india betesmellitus with respective age group. To investigate metabolic changes in Diabetesmellitus, following parameters were studied in blood.
Study included 50 clinically diagnosed case of diabetesmellitus irrespective of age ands ex who admitted to the Government Medical College, Aurangabad and 50 normal controls not having DM. Laboratory investigation sin diabetes mellitus Blood sugar estimation, oral glucose to lerance test and urinary sugars were used for diagnosis and monitoring of diabetic patients. In addition sample were analysed for the study of glycated hemoglobin, serumenzymes, total proteins, amino acid pool. 10 ml of blood was drawn from clinically diagnosed cases of DM under asepticprecautionusing15 mldisposable syringe after taking written consent.3 separate test tubes were taken and labeled themas1,2,3. Test tube1was utilized for the estimation of blood glucose where in 2ml of blood was mixed with anticoagulant which was done by glucose oxidation method. Test tube 2 was utilized for them measurement of total proteins, AST, ALT, albuminin which 3ml of blood with noanti-coagulant that was allowed to clot and serum was separated. Test tube 3 was utilized for the estimation of glycosylated haemoglobin in which 1ml of whole blood was taken for affinity chromatography. Blood Glucose levels were assessed by Trinder’s method, total protein levels were assessed by Biuret method. Albumin was assessed by Bromo Cresol Green Dye (BCG) method. Alanineamino transferase or SGPT was measured by IFCC (International Federation of Clinical Chemist) kinetic method. AST or SGOT was measured by IFCC kinetic method. Estimation of aminoacid nitrogen was done by method of Goodwin.
RESULTS A Comparative study with 50 subjects in non-diabetic controls and 50 subjects in freshly detected diabetics is undertaken to study the sugar levels in non-diabetic controls and freshly detected diabetic.
Table 3: Levels of study parameters in Control and Freshly detected diabetics
DISCUSSION Diabetes mellitus is the most common metabolicde generating disease affecting mainly carbohydrate, lipid and protein metabolism. Diabetes mellitusis mainly due to insulin deficiency or insulin resistance. Insulin beings sananabolichormoneits deficiency cause shyperglyc emia due to increased gluconeogenesis and glycogenolys is and it affects lipid and protein metabolism by causing increased lipolys is which leads to ketosis and ketoacidos is and it affects overall protein biosyn thesis which causes increased circulating amino acid pool. In our study we took 17cases of freshly detect diabetic patients and 17 cases of age and sex matched healthy controls. Freshly detected diabetics were chosen because as the study parameters will not be altered due to the rapeuticinter venations. Blood glucose Insulin plays a central role in regulating blood glucose (H). Deficiency of insulin or resistance to the action of insulin as seen in the diabetesme llitusis characterized by hyperglycemia. According to WHO criteria FBS126mg/dlon2 occasionsis diagnostic of diabetes mellitus (teitz). Randombloodglucose200mg/dlon2 occasionsis also diagnostic of diabetes mellitus. In our study theme an FBS values of the patients was182.21mg/dl diagnostic of diabetes mellitusand the PPBS was214.4mg/dl which is high erthanupperlimitcut of f value of 140mg/dl where as control group had blood glucose valuesas95.36 and1.33.14 for FBS and PPBS respectively suggestive normal glycemia. These values correlate well with clinical diagnosis. Glycated heamoglobin Measument of HBA1 cisdonetomonit or the control of blood glucosein diabetes mellitus. Alterationin blood glucoseoccurs from day today depending on the dietaryin take. The Glycated haemoglobin values give the average blood glucose level of preceding2-3months.Various studies have shown that amount of glucose attached to HBA1cincreases within crease duration of DM. Meena Verma and et al, in the restudy showed within crease duration of diabetes mellitus, the HbA1cvaluealso increased indicating increased insulin resistance. In another study done on libian women, it was found that there was a significant correlation between HbA1C and duration of DM. In our study theme an Glycated haemoglobin level of patients was 11.03%in comparison to the controls with mean of 5.12 In study done by Krolewski AS, et al, it was shown that the risk of micro albuminuriain patients with IDDM increased abruptly with Glycatedhemoglobin above8.1%. Amino Acid Pool And Serum Protiens Many studies have reported that insulin play sakeyrolein maintaining the aminoacid level in blood in addition to its in regulating break down and synthesis of many proteins. Insulin may enhancesyn thesis rate of proteins by increasing translation of m RNA as well as increasing the gene transcription. In patients with type1DM, withdrawal of insulin treatment results in increased urinary nitrogen loss and in increasing circulating aminoacid level. The circulating levels of branch edchainaminoacids (valin, leucin, isoleucin) increases in DM. The observed effects insulin deficiency in diabetic patients vary indifferent body compartments, most of the effects of insulin on protein synthesis appear to occur in nonmuscular tissue especially in the splanchnicarea. In addition, insulin has a differential effect on hepatic protein synthesis, It in hibits fibrinogensyn thesis and Promote salbuminsyn thesis. Insulins anticatabolic effect in IDDM patients is largely due to inhibition of protein break down. In patients with NIDDM, these effects are not noted because of residential endogenous insulin secretion. Diabetes mellitusis thus characterized by accelerated protein catabolism and aminoacid catabolism which is exaggerated in fasting stateasref lected by increased up take of alanine by the liver for gluconeogenes is and accelerated branched chain aminoacid catabolis minmuscles. Protein feeding also exaggerates the hyperglycemia of DM by causing increased hepaticglucose production. In our study the mean aminoacid level in patients is 12.23, mean total protein valueis 5.26, meanalbuminis 4.69 and meanglobulin level of patients is 1.89.There is increase in amino acid level and decrease in A/Gratio thus affecting protein metabolism. Astandalt Enzymes Duemetabolicderangements in DM, level of serumenzymes of protein metabolism is affected. The enzymesmainly AST and ALT were elevated indirectly due to either acute tissue damage or caused due to metabolic complication of DM. It is usually seen in post ketoticperiod. Francesco Beltlone, Lulgi Lovuchio and Elena Nepoli studied several erumenzymesin DM; they showed that AST and ALT enzymes were elevated indirectly. In another study by Gold bergetal, it was shown that, 17% of these patients had increased ALP activity, 15% had raised AST activity and 12% haincreased LDH activity. CONCLUSION Diabetes mellitusisade generating disease affecting carbohydrate metabolism consequent to which lipid and protein metabolism are also affected. In DM due to insulin deficiency overall body protein synthesis is affected, which is reflected in concentration of aminoacids in circulating aminoacid pool. These change sare more pronounced with advance in age. It was observed that in DM, the circulating aminoacid content increases compared to normal patients. This is proportional to increase in percentage of Glycated H band other parameter like Tp, Albumin, A/Gratioandserumenzymes AST, ALT showed decrease level. Freshly detected DM is associated with statistically significant increase in aminoacid pool and Glycatedhemoglobin and decrease in parameters like Total protein, Albumin, A/Gratioandserumenzymes AST, ALT level.
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