Diabetess mellitus is a metabolic upset characterized by chronic hyperglycaemia, that is, high blood glucose due to derangement in saccharide, fat, and protein metamorphosis that are associated with absolute or comparative lacks in insulin secernment, insulin action or both 1,2. The insulin endocrine is responsible for modulating blood glucose. Diabetes is a chronic wellness status that can take to several other medical jobs if non managed decently 3. Diabetic patients usually present symptoms such as polyuria ( frequent micturition ) , polydipsia ( increased thirst ) and polyphagia ( increased hungriness ) and weight loss.
In America, estimated new instances of diabetes diagnosed each twenty-four hours are 1,800, or about 655,000 new instances each year6. Harmonizing to the World Health Organization ( WHO ) , diabetes affects more than 170 million people worldwide, and this figure will lift to 370 million by 2030 9,10. In Zimbabwe, though there is deficiency of current statistics on the disease and its prevalence, diabetes is among the top five chronic conditions seen in the out-patients clinic. The latest study was done in 2005 which noted that the prevalence of diabetes among the grownup population was 10 % with a big figure of people non cognizant that they had raised blood sugar degrees.
Diabetess mellitus is classified chiefly into Type I and Type II, which are the chief groups, gestational diabetes and diabetes secondary to other diseases and conditions such as, following pancreatic surgery.
Type I is the insulin dependent diabetes mellitus which is chiefly idiopathic ( do unknown ) or caused by autoimmune upsets. This status arises because of an absolute insulin lack due to devastation of islet cells in the pancreas.4 This group comprises of less than 10 % of patients who are diabetic 2,3,4. The oncoming is normally acute, developing over a period of a few yearss to hebdomads. Over 95 per centum of individuals with type I Diabetes mellitus develop the disease before the age of 25.
Type II Diabetes mellitus arises from deficient production of the endocrine insulin from beta cells of the pancreas and in conditions where the peripheral receptors ; chiefly musculuss, liver and fat tissue, do non react adequately to normal insulin degrees, known as insulin resistance.4 Alternatively of change overing glucose into energy, glucose dorsums up into the blood stream. This group makes up approximately 90 % of instances of diabetes and has a slow and insidious onset.2,11 It normally occurs in people who are over 40 old ages of age, fleshiness, sedentary life manner, hapless diet, high blood pressure and have household history of diabetes. It is besides common in adult females particularly those with a history of gestational diabetes, which is defined as any grade of glucose intolerance which onset or first recognized during gestation. It was once known as grownup onset but now it is progressively found in immature people particularly in the 21st Century.3,5 The epidemiological information shows that approximately 80 % of Type II diabetic patients are considered to be corpulent, holding a organic structure mass index ( BMI ) greater than or equal to 30 kg/m2, whereas the other 20 % are above their ideal weight or have a BMI of 25 to 29.9 kg/m2. 7 Diet entirely can be used as a manner of commanding Type II diabetes or by a combination of medicines ( unwritten hypoglycemics or insulin ) , exercising, and diet.8
A survey by the Nigerian National Non-Communicable Disease Survey, reported a prevalence rate of about 2.2 % for diabetic mellitus with over 90 % Type II diabetics in Nigeria. Epidemiological information shows there are increasing incidences of Type II Diabetic mellitus and diabetic patients are at an increased hazard of developing complications such as: kidney disease, retinopathy, neuropathy and atherosclerosis 3,8,13. This has made it go a planetary wellness concern since about one tierce of Type II will finally hold progressive impairment of nephritic map 10,11.
Kidneies are a brace of critical bean-shaped variety meats in the organic structure. In grownups each kidney is about 10-14 centimeter in length, 6 centimeter in breadth and is 4 centimeter midst. Each weighing about 150 grammes.14 They are located at the rear of the abdominal pit in the retroperitoneum merely below the rib coop one on each side of the spinal column. The chief map of kidneys is to have blood from the mated nephritic arterias and run outing it into the mated nephritic venas. Kidneys are an indispensable portion of the urinary system and besides serve homeostatic maps such as the ordinance of electrolytes, care of acid-base balance, and ordinance of blood force per unit area 14. The kidneys are one of the most of import sophisticated variety meats in the organic structure which chiefly serve as a natural filter of the blood maintaining the organic structure chemically balanced. They remove waste which is diverted to the urinary vesica. In bring forthing piss, the kidneys excrete nitrogen-bearing wastes such as urea, creatinine, uric acid, ammonium, other acids, electrolytes and excess H2O. The kidneys besides are responsible for the resorption of H2O, glucose, and aminic acids.
A normal individual ‘s kidneys process about 150 liters of blood to sift out of the organic structure about 1500 milliliter of waste merchandises produced by metamorphosis procedures daily15. The existent filtering of wastes occurs in bantam units inside the kidneys called uriniferous tubules which are the urine-producing functional constructions of the kidney. Each kidney has about a million functional uriniferous tubules, crossing the cerebral mantle and myelin 14,15. The initial filtering part of a uriniferous tubule is the nephritic atom ( glomerulus ) , located in the cerebral mantle, which is followed by a nephritic tubule that passes from the cerebral mantle deep into the medullary pyramids.
Kidney failure is when kidneys are no longer able to take and keep the degree of fluid and salts that the organic structure needs. Diabetes mellitus frequently amendss the kidneys particularly when the disease is non controlled by maintaining blood glucose degrees within the normal scope.
1.3 Diabetic kidney disease
Diabetic kidney disease is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli16. Diabetes mellitus is a stipulation for developing two major early glomerular lesions, glomerular cellar membrane ( GBM ) thickener and mesangial enlargement which are non present at the diagnosing of diabetes but are found 2 to 5 old ages after oncoming of hyperglycaemia 17. The disease is progressive and may do decease two or three old ages after the initial lesions, and is more frequent in men18 than in adult females because of differences in life style and testosterone lack that is common in work forces who are diabetic.37
Diabetic kidney disease is the most common cause of chronic kidney failure and End Stage Kidney Failure ( ESRD ) throughout the universe in both developed and emerging states 16,19. In 1991, it was estimated that diabetes accounted for 40 % of the freshly diagnosed instances of ESRD20.Normally 10 to 20 old ages after oncoming of open nephropathy about 20 % will come on to ESRD since the rate of autumn is extremely variable from single to single. 21,22,23 Patients with Diabetes mellitus should be diagnosed early for nephropathy since they are at a high hazard, this will assist them in forestalling the development or patterned advance of diabetic nephropathy.24
Progressive nephritic disease is caused by the combination of an initial or on-going hurt and a concluding common tract of mal-adaptive response to that hurt, a response that involves alterations in glomerular hemodynamics and the release of cytokines and vaso-active endocrines 25,26.
Pathogenesis of diabetic kidney disease
The patterned advance of diabetic kidney disease is divided into 5 stages.26 In phase I there is hyperfiltration. 26,27,28 Hyperglycaemia causes unnatural glycosylation of cellular proteins which through a series of chemical reactions evolve to organize Advanced Glycation End-Products ( AGEs ) . AGEs can bring on unnatural cellular alterations by signalling through receptors which are expressed by cells in the gromerulus. This unnatural signalling may interrupt of import paracrine signalling between podocytes and endothelial cells required for normal maintaince of the filtration membrane, therefore detrimental uriniferous tubules. Hyperglycaemia can besides excite formation of O groups that besides damage uriniferous tubules doing loss of working uriniferous tubules. The kidneys in healthy persons try to counterbalance for damaged uriniferous tubules by increasing the Glomerular Filtration Rate ( GFR ) in order to keep homeostasis. In order to make this, the kidney secretes intra-renal vaso-active endocrines, such as prostaglandin E2, that preferentially dilate afferent arteriolas and other endocrines such as angiotonin and catecholamines constrict motorial arteriolas. Each glomerulus hence receives more blood at a higher force per unit area and therefore filters more unstable into tubules. This in bend overworks and amendss the glomerular capillary in elusive ways. It causes mesangial cell and glomerular cellar membrane hurt, and stimulates release of cytokines. All of these effects can bring forth farther grim hurt and scarring of the staying uriniferous tubules with farther uriniferous tubule loss, systemic high blood pressure and albuminuria. Systemic high blood pressure, in the scene of a glomerulus with dilated sensory nerve and constricted motorial arteriolas and unnatural cellar membrane permeableness causes even greater grades of glomerular force per unit area and hurt 25.
Hyperfiltration has been shown to be present in early stages of diabetes, may be for several old ages. 25,27,28 Unfortunately, there are no symptoms during the hyperfiltration phase. However, with early sensing and proper glycemic control, hyperfiltration is reversible.26,28 Lowering blood force per unit area, irrespective of the type of agent used to make so, idiots the oncoming and patterned advance of diabetic nephropathy.22,28 However, hyperfiltration does non ever predict the hereafter development of kidney hurt in diabetes.26
During phase II, the damaged capillaries allow little sums of albumen to be excreted in the piss. Between 13 % and 41 % of people have microalbuminuria when foremost diagnosed with type II diabetes.27,28 Persons may stay in this phase for several old ages by accomplishing proper control of blood glucose degrees and blood pressure.26 In this phase GFR begins to diminish as microalbuminuria appears. Although the overall GFR is decreased, the glomerular filtration rate per uriniferous tubule is increased, and hyperfiltration hurt continues. This leads to farther uriniferous tubule loss, albuminuria, glomerular and interstitial scarring, and progressive nephritic failure.
Phase III is when diabetic kidney disease is first noticeable.26,28 There is accretion of waste merchandises in the blood which is known as uremia, some which are toxic. At this phase degrees of creatinine and Blood Urea Nitrogen ( BUN ) increase.26 There is besides a loss of molecules such as albumen and glucose in piss which are non supposed to be lost in healthy conditions. Early sensing at this phase is critical to continue kidney map and to detain or forestall ESRD.33 Type II diabetes patients may stay in this phase for several old ages with proper glycemic control.26
Phase IV is the point when kidney harm is irreversible and is normally known as advanced clinical nephropathy.26 At this phase, due to reduced surface country in kidneys, they will no longer be capable of egesting toxins and consequently there is a progressive addition in BUN and creatinine levels.11,29 Most people in this phase are hypertensive secondary to increased production of renin. Because high blood pressure accelerates the patterned advance to ESRD, early sensing is vital.30 If non treated at this phase ; uremia and decease will follow within 7 to 10 years.31
Phase V or ESRD, is when the kidneys fail to map, the overall GFR badly decreased, and high blood pressure continues to worsen.32 During this concluding phase, the kidneys can non egest toxins ; keep fluid, pH, and electrolyte balances ; or release of import endocrines ( renin, vitamin D, and erythropoietin ) . As a consequence, a battalion of symptoms become evident that involve most major organ systems in the body.30
Creatinine is a byproduct of creatine, a merchandise produced from musculus. Creatinine is filtered by the glomerulus ; hence, serum creatinine degree can be used as an indirect step of glomerular filtration. As GFR diminishes, there is a rise in plasma concentrations of serum creatinine and urea.11 At the early phase of kidney disease, serum creatinine corsets within normal scope due to strong kidney compensatory abilities. When creatinine begins to lift, the kidneys would hold been badly impaired, helpful in tracking the patterned advance of diabetic kidney disease. Ill controlled diabetes can impair glomerular cellar membrane.33 Normal serum creatinine is normally 0,6 – 1,1 mg/dl for adult females and 0,7 – 1.3 mg/dl for men.34
1.5 Blood Urea Nitrogen
Blood Urea Nitrogen ( BUN ) is a waste merchandise produced after protein metamorphosis excreted as piss. It is parameter to name the functionality of the kidney 35. It is a rather sensitive index of nephritic disease, going elevated when nephritic map beads to around 25-50 % of normal.36 Normally carbamide is filtered out of the blood and controlled to a scope of 8 -24 mg/dl for work forces and 6 – 21 mg/dl for adult females 34. BUN and creatinine are the simplest manner to supervise kidney map.
1.6 Statement of job
Diabetess mellitus has rapidly become a planetary wellness job due to quickly increasing population growing, aging, urbanisation and increasing prevalence of fleshiness and physical inaction 33. Intensive direction of blood sugar is a intervention government that aims to maintain glucose concentration within normal scope forestalling patterned advance of diabetic complications. Diabetic nephropathy occurs about in one tierce of type 2 diabetic patients 8,11,12 and is on the rise. This survey aims to find urea and creatinine concentrations in type II diabetic patients go toing Parirenyatwa Diabetic clinic. Results obtained will bespeak if intervention they are having is efficaciously pull offing the patients to cut down the hazard of nephritic harm.
To measure creatinine and urea concentration in Type II diabetic patients go toing Parirenyatwa Diabetic Clinic.
To measure the progressive impairment of nephritic map in type II diabetic patients go toing Parirenyatwa Diabetic Clinic.
Null hypothesis ( H0 ) : Less than one tierce of type II diabetic patients have elevated values of urea and creatinine.
Alternate hypothesis ( H1 ) : more than one 3rd if type II diabetic patients have elevated values of urea and creatinine.
Chapter Two: Materials AND METHODS
Refer to appendix
2.2. Study site
The undertaking was conducted at Parirenyatwa Group of Hospitals Diabetic Clinic.
2.3 Study design.
A research lab based cross-sectional survey was carried out on the serum samples of diabetic patients go toing the Diabetic Clinic at Parirenyatwa Group of Hospital ( PGH ) .
2.4 Study topics
Patients who have been documented as diabetics for at least 12 months who routinely attend Parirenyatwa Group of Hospitals Diabetic Clinic.
Patients with a history of kidney jobs and congestive cardiac failure were excluded from the survey.
Pregnant adult females, tobacco users and hyperlipidemics
Patient drug history were elucidated to avoid falsely elevated consequences due to nephrotoxic drugs consequence, such as aminoglycosides, Tagamet, cefoxitin, heavy metal chemotherapy drugs and nephrotic drugs14 etc..
2.5 Ethical considerations
Permission to transport out the undertaking was sought from governments in charge of the Diabetic Clinic, the Consultant and the ward director.
Ethical blessing was sought from the Joint research Ethics Committee of the College of Health Sciences and Parirenyatwa Group of Hospitals ( JREC/346/12 )
2.6 Sample size
The sample size ( n ) was calculated to be 239 samples ( mention to appendix for computation ) utilizing the premise that kidneys of one tierce of type II diabetic patients deteriorates in map.
aggregation of sample
Residual samples left during everyday testing of type II diabetic patients who have been on intervention for more than 12 months were used. Besides residuary samples from topics with normal nephritic map trials and random blood glucose were besides collected.
2.7.2 Sample designation and patient confidentiality
After permission from the Diabetic Clinic at Parirenyatwa Group of Hospitals, Public Health Laboratories and the ethical blessing from Joint Research Ethics Committee of the College of Health Sciences was given, samples were collected and de-identified for confidentiality by giving numeral codifications E001… , to E239 [ This is portion of Ethical considerations ] .
2.7.3Procedure of the survey
Samples were centrifuged at 3 000 revolutions per minute ( revolutions per minute ) . The serum was aliquoted into plastic made serum pots utilizing a micropipette to divide with cells and so stored in a icebox at a temperature maintained between 2 – 8 oC. Prior to processing of the samples they are brought to room temperature and the analyzer was calibrated. After standardization the control samples were run as a quality control step to do certain the analyzer was working as expected. Samples were so processed in batches. The samples were loaded in the sectors of the machine ( Mindray BS 120 ) and assayed for urea and creatinine.
2.7.4 Principle of trials
Appraisal of plasma creatinine was done utilizing modified Jaffe ‘s method 9-10. Serum carbamide was estimated utilizing the Urease-glutamate Dehydrogenase, UV method.
The rule of Jaffe ‘s method
Creatinine + Picric acid OH- Creatinine-picric acid composite
At an alkalic solution, creatinine combines with picric acid to organize an orangish-red colored composite. The absobency addition is straight relative to the concentration of creatinine. This method is done utilizing an optical density of 510nm.
The rule of Urease-glutamate Dehydrogenase, UV method
Urea + 2H2O urease 2 NH4+ + CO2 2-
?-Oxoglutarate +NH4+ + NADH GLDH L-Glutamate + NAD+ +H2O
Urea is hydrolysed by urease, and one of the merchandises, ammonium hydroxide, helps to turn NADH to NAD+ with the contact action of GLDH. The absorbency lessening is straight relative to the concentration of urea. This is measured at 340nm.