The Biochemical Effects of Cussonia Arborea Root Bark Extract in Alloxan-Induced Diabetic Rats

Filed in Zoology Project Topics by on July 7, 2021

The Biochemical Effects of Cussonia Arborea Root Bark Extract in Alloxan-Induced Diabetic Rats.

 ABSTRACT

Diabetes mellitus is a group of metabolic disorders characterized by chronic hyperglycemic conditions resulting from defects in insulin secretion, insulin action, or both. It is a growing public health concern worldwide affecting humans and animals. Synthetic drugs available for the treatment of the ailment have serious side effects, complicated mode of intake, and are costly.

A literature search revealed that Cussonia Arborea is used folklorically in the management of Diabetes mellitus. The aim of this study is to isolate, characterize and elucidate the active principle responsible for its hypoglycaemic activity using alloxan-induced diabetic rats.

The root bark of C. Arborea (2 kg) was extracted with 80% methanol by the cold maceration method. An acute toxicity study was done in 35 rats assigned into 7 groups of 5 rats per group. Groups 1, 2,3,4,5, and 6 rats were orally administered with graded doses (500, 1000, 2000, 3000, 4000, 5000 mg/kg bw) of the extract respectively.

The rats in group 7 received 10 ml/kg distilled water (DW) to serve as a negative control group. They were observed closely for 48 hours for signs of toxicity. Assessment of hypoglycemic activities of the extract was done using oral glucose tolerance test (OGTT), acute and chronic antidiabetic studies.

In OGTT, 30 rats were randomly assigned into 5 groups of six rats per group. Groups 1, 2, and 3 rats received 250, 500 and 1000 mg/kg bw of the extract respectively while groups 4 and 5 rats received 2 mg/kg bw glibenclamide and 10 ml/kg DW respectively after 18 h fasting and prior to 2000 mg/kg of the glucose load. The fasting blood glucose (FBG) levels of the rats were determined after 30, 60, 120 and 180 min post glucose challenge.

Diabetes was induced by single intraperitoneal administration of alloxan monohydrate at the dose of 160 mg/kg bw. Rats with FBG levels above 126 mg/dl (7 mMol/L) were considered diabetic. Thirty male albino Wistar rats assigned into 6 groups of 5 rats per group were used for acute antidiabetic studies.

Groups 1, 2, 3, 4, and 5 were diabetic rats treated with 250, 500 1000 mg/kg bw of the extract, 2 mg/kg bw glibenclamide, and 10 ml/kg DW respectively while group 6 rats were nondiabetic but administered with 10 ml/kg DW.

The FBG levels of the rats were determined 1 h, 3 h, 6 h, and 24 h post-treatment. Seventy-two (72) male albino wistar rats weighing between 100 and 105 g were assigned into six groups of 12 rats per group for chronic antidiabetic studies. Groups 1, 2, 3, 4 and 5 rats were made diabetic as described earlier and treated with 62.5, 125, 250 mg/kg bw of the extracts, 2 mg/kg bw glibenclamide and 10 ml/kg DW respectively while the nondiabetic group 6 rats received 10 ml/kg DW and served as normal control rats.

The treatment was daily through the oral route for 84 days. The biochemical (aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, triglyceride, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), total protein, albumin, globulin, blood urea nitrogen, creatinine, total bilirubin, conjugated bilirubin, unconjugated bilirubin, malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and reduced glutathione) and hematological (red blood cell (RBC), hemoglobin (Hb), packed cell volume (PCV), white blood cell (WBC), differential leucocytes (lymphocytes, neutrophils, basophils, eosinophils, and monocytes), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC)) parameters were assayed on days 28, 56 and 84 post-treatment while the FBG values and weight changes were determined every two weeks.

The glycosylated hemoglobin values were measured on days 42, 56, and 84 post-treatment. Three rats per group were humanly sacrificed on days 28, 56, and 84 for the assessment of the histomorphology of various organs (pancreas, kidney, liver, and heart).

In vitro, the antioxidant assay was carried out using ferric reducing antioxidant power (FRAP) and diphenyl picryl hydroxyl (DPPH) photometric essay models. Chromatographic separation of the plant extract was done using column and thin layer chromatographic techniques.

The 1H proton and 13carbon nuclear magnetic resonance (NMR) were used for structural elucidation of the active hypoglycaemic principle. No sign of toxicity was observed after the acute toxicity test. The phytochemical analysis revealed the presence of alkaloids, flavonoids, glycosides, saponins, tannins, and terpenes.

The mean FBG level of the rats treated with 250 mg/kg bw of the extract in the acute anti-diabetic study, at 3 h post extract administration was significantly (p<0.05) lower than the FBG before administration of the extract. In the chronic anti-diabetic study, the mean FBG level of rats treated with 125 mg/kg bw of the extract reduced significantly (p<0.05), the post-induction FBG from 315.33± 10.08 mg/dl to 93.00 ±8.50 mg/dl, 14 days post-administration and ameliorated the glycosylation of hemoglobin compared to the negative control group.

Administration of 250 mg/kg bw of the extract in glucose challenged rats reduced the post-challenge glucose level from 147.66 ±1.85 mg/dl to 83.00 ±3.5 mg/dl, 180 min post-treatment.

Assessment of the biochemical and hematological parameters in chronically-treated diabetic rats showed that the administration of 125 mg/kg bw of the extract, significantly (p<0.05) reduced the activities of AST, ALT and the levels of total cholesterol, triglyceride, VLDL, LDL BUN, creatinine, total bilirubin, malondialdehyde but significantly (p<0.05) increased the activities of SOD, catalase and the levels of HDL, total protein, conjugated bilirubin, reduced glutathione, RBC, Hb, and PCV when compared to the diabetic untreated group (negative control). The extract yielded seven fractions.

The FBG of the rats treated with 12.5 mg/kg bw of fraction 2 was significantly (p<0.05) lower compared to the negative control group. Subfraction 1 (2 mg/kg) of fraction 2 significantly (p<0.05) reduced the FBG levels from 310.00±5.77 mg/dl to 74.00±0.57 mg/dl. Rats treated with 125 mg/kg bw of the extract showed milder histopathologic lesions in various tissues compared with negative control.

The DPPH in vitro antioxidant assay showed concentration-dependent activities with 400 µg/ml of the extract and ascorbic acid showing 74% and 92% activities respectively. The FRAP values of the extract and ascorbic acid at 400µg/ml were 1.60 and 2µm respectively. The NMR spectroscopy revealed a pentacyclic triterpenoid, {(3β)-3-hydroxyolean- 12-en-28-oic acid} as the active compound.

The study showed that the root bark extract of C. Arborea did not only possess antihyperglycaemic, hypolipidemic, antioxidant, and antianemic properties but also reduced hemoglobin glycosylation and ameliorated the severe degenerative lesions in the pancreas, kidney, liver and cardiac myocytes occasioned by Diabetes mellitus.

 

TABLE OF CONTENTS

Title page ———————————————————————————————– —–i
Certification ——————————————————————————————– —–ii
Dedication ———————————————————————————————- —-iii
Acknowledgments ———————————————————————————— —-iv
Table of contents ————————————————————————————– —-vi
List of figures——————————————————————————————–xix
List of plates———————————————————————————————xxi
List of tables——————————————————————————————–xxiv
Appendix———————————————————————————————–xxviii
Abstract————————————————————————————————- -xxix

CHAPTER ONE
1.1 Introduction —————————————————————————————- 1
1.2 Background of the study ————————————————————————- 10
1.3 Statement of the problem————————————————————————- 11
1.4 Objectives of the study ————————————————————————— 11

CHAPTER TWO
2.0 Literature review ———————————————————————————- 12
2.1 History of Diabetes mellitus ——————————————————————— 12
2.2 Prevalence and incidence of Diabetes mellitus———————————————— 13
2.3 Classification of Diabetes mellitus————————————————————– 13
2.3.1 Type 1 Diabetes mellitus———————————————————————– 18
2.3.1.1 Autoimmune type Diabetes mellitus——————————————————– 18
2.3.1.2 Idiopathic type 1 Diabetes mellitus——————————————————— 19
2.3.1.3 Pathogenesis of type 1 Diabetes mellitus ————————————————– 19
2.3.2 Type 2 Diabetes mellitus———————————————————————– 21
2.3.2.1 Pathogenesis of type 2 Diabetes mellitus ————————————————– 21
2.3.3 Gestational Diabetes mellitus—————————————————————— 22
2.3.3.1 Pathogenesis of gestational Diabetes mellitus——————————————— 23
2.3.3.2 Diabetogenic potency of pregnancy hormones——————————————– 23
2.3.4 Other specific types—————————————————————————- 24
2.3.4.1 Genetic defects of beta-cell function——————————————————– 24
2.3.4.2 Genetic defects in insulin action ———————————————————— 25
2.3.4.3 Diseases of exocrine pancreas————————————————————— 25
2.3.4.4 Endocrinopathies —————————————————————————– 26
2.3.4.5 Drug or chemical induced Diabetes mellitus ———————————————- 26
2.3.4.6 Infection ————————————————————————————— 26
2.3.4.7 Other genetic syndromes associated with Diabetes mellitus—————————– 27
2.3.5 Type 3 Diabetes mellitus (Alzheimer’s disease) ——————————————– 28
2.4 Clinical signs of Diabetes mellitus————————————————————– 28
2.5 Complications of Diabetes mellitus————————————————————- 30
2.5.1 Acute complications—————————————————————————- 30
2.5.2 Chronic complications————————————————————————– 33
2.6 Diagnosis of Diabetes mellitus —————————————————————— 37
2.6.1 Formation of glycosylated hemoglobin —————————————————– 38
2.6.2 Criteria for diagnosing Diabetes mellitus —————————————————- 40
2.6.3 Oral glucose tolerance test——————————————————————— 42
2.7 Management and treatment of Diabetes mellitus———————————————- 44
2.7.1 Pharmacologic intervention——————————————————————– 44
2.7.1.1 Use of oral hypoglycemic/antidiabetic drugs——————————————— 44
2.7.1.1.1 Sulfonylurea——————————————————————————— 44
2.7.1.1.2 Biguanides———————————————————————————– 48
2.7.1.1.3 Thiazolidinediones ————————————————————————- 50
2.7.1.1.4 Meglitinides——————————————————————————— 54
2.7.1.1.5 Incretin-mimetics————————————————————————— 58
2.7.1.1.6 Alpha-glucosidase inhibitors ————————————————————– 61
2.7.1.2 Insulin therapy ——————————————————————————– 61
2.7.1.3 Injectable amylin analog —————————————————————— 62
2.7.1.4 Glycourics ————————————————————————————- 63
2.7.1.5 Medicinal plants with antidiabetic properties ——————————————— 63
2.7.2 Non pharmacologic interventions————————————————————- 66
2.7.2.1 Exercise —————————————————————————————- 66
2.7.2.2 Diet ——————————————————————————————— 69
2.8 Experimental diabetes —————————————————————————- 70
2.9 Chromatography———————————————————————————– 72
2.10 Spectroscopic techniques ———————————————————————– 73
2.11 Cussonia arborea——————————————————————————– 74
2.11.1 Scientific classification of Cussonia arborea ———————————————- 74
2.11.2 Different local names of the plant ———————————————————– 78
2.11.3 Geographical distribution of the plant——————————————————- 78
2.11.4 Folkloric uses of Cussonia arborea ——————————————————— 79

CHAPTER THREE
3.0 Materials and Methods ————————————————————————— 80
3.1 Materials ——————————————————————————————- 80
3.1.1 Chemicals and reagents ———————————————————————— 80
3.1.2 Instruments and glasswares——————————————————————– 80
3.1.3 Animal ——————————————————————————————- 81
3.1.4 Plant ———————————————————————————————- 82
3.2 Methods——————————————————————————————– 82
3.2.1 Preparation of the plant extract—————————————————————- 82
3.2.2 Acute toxicity test——————————————————————————- 83
3.2.3 Induction of experimental diabetes ———————————————————– 83
3.2.4 Dose response study —————————————————————————- 83
3.2.5 Antioxidant test ——————————————————————————— 84
3.2.6 Oral glucose tolerance test——————————————————————— 86
3.2.7 Phytochemical tests—————————————————————————– 86
3.2.8 Chronic antidiabetic study ——————————————————————— 88
3.2.9 Glycosylated haemoglobin assay————————————————————– 89
3.2.10 Serum biochemistry determinations——————————————————— 91
3.2.10.1 Determination of serum aspartate aminotransferase ———————————— 91
3.2.10.2 Determination of serum alanine aminotranferase—————————————- 93
3.2.10.3 Determination of serum protein ———————————————————– 95
3.2.10.4 Determination of serum albumin ———————————————————- 95
3.2.10.5 Determination of serum globulin ———————————————————- 96
3.2.10.6 Determination of serum total cholesterol————————————————- 96
3.2.10.7 Determination of serum HDL-Cholesterol ———————————————– 97
3.2.10.8 Determination of serum triglyceride —————————————————— 98
3.2.10.9 Determination of serum bilirubin———————————————————- 98
3.2.10.10 Determination of serum creatinine——————————————————- 99
3.2.10.11 Determination of blood urea nitrogen (BUN) —————————————— 100
3.2.11 Haematologic determinations —————————————————————- 101
3.2.11.1 Determination of packed cell volume —————————————————– 101
3.2.11.2 Determination of hemoglobin concentration——————————————– 102
3.2.11.3 Determination of erythrocyte count——————————————————- 102
3.2.11.4 Determination of total leucocyte count ————————————————— 102
3.2.11.5 Determination of differential leukocyte count ——————————————- 103
3.2.11.1 Determination of mean corpuscular values———————————————– 103
3.2.12 In vivo antioxidant assay———————————————————————- 103
3.2.12.1 Assay of superoxide dismutase activities————————————————- 103
3.2.12.2 Estimation of catalase activities ———————————————————– 105
3.2.12.3 Determination of reduced glutathione values ——————————————– 106
3.2.12.4 Determination of malondialdehyde levels———————————————— 107
3.2.13 Histopathology examination —————————————————————– 107
3.2.14 Bioassay-guided fractionation/isolation of active compound —————————- 109
3.2.14.1Column chromatography——————————————————————– 109
3.2.14.2 Thin layer chromatography —————————————————————- 111
3.2.14.3 Bio-assay guided screening of the fractions———————————————- 112
3.2.14.4 Preparative thin layer chromatography ————————————————— 113
3.2.14.5 Purification of the active fraction———————————————————- 114
3.2.14.6 Characterization and structural elucidation ———————————————- 114
3.2.14.7 Statistical analysis————————————————————————— 115

CHAPTER FOUR
4.0 Results———————————————————————————————- 116
4.1 Percentage yield ———————————————————————————– 116
4.2 Acute toxicity————————————————————————————– 116
4.3 Phytochemical test ——————————————————————————- 116
4.4 Percentage antioxidant activity (FRAP) ——————————————————– 116
4.5 Percentage antioxidant activity (DPPH)——————————————————– 120
4.6 Effect of acute administration of C.arborea root bark extract on fasting blood glucose (FBG) levels of alloxan-induced diabetic rats—————————————- 120
4.7 Effect of C.arborea root bark extract on normoglycemic rats (OGTT)——————— 120
4.8 Effect of chronic administration of C.arborea root bark extract on FBS levels of alloxan-induced diabetic rats —————————————————- 124
4.9 Effect of different fractions of C.arborea on FBG levels of alloxan-induced diabetic rats ———————————————————– 124
4.10 Effect of different fractions of C.arborea on the FBG levels of alloxan-induced diabetic rats ——————————————————– 124
4.11 Glycosylated haemoglobin values of alloxan-induced diabetic rats administered with methanol root bark extract of C.arborea—————————- 128
4.12 Effect of chronic administration of C.arborea root bark extract on the activity of aspartate aminotransferase of alloxan-induced diabetic rats ———- 128
4.13 Effect of chronic administration of C.arborea root bark extract on the activity of alanine aminotransferase l of alloxan-induced diabetic rats ———— 131
4.14 Effect of chronic administration of C.arborea root bark extract on total cholesterol of alloxan-induced diabetic rats—————————————– 131
4.15 Effect of chronic administration of C.arborea root bark extract on serum triglyceride of alloxan-induced diabetic rats————————————— 134
4.16 Effect of chronic administration of C.arborea root bark extract on high density lipoprotein of alloxan-induced diabetic rats——————————– 134
4.17 Effect of chronic administration of C.arborea root bark extract on very low density lipoprotein of alloxan-induced diabetic rats————————— 134
4.18 Effect of chronic administration of C.arborea root bark extract on low density lipoprotein of alloxan-induced diabetic rats——————————– 138
4.19 Effect of chronic administration of C.arborea root bark extract on total protein of alloxan-induced diabetic rats———————————————- 138
4.20 Effect of chronic administration of C.arborea root bark extract on albumin of alloxan-induced diabetic rats————————————————– 138
4.21 Effect of chronic administration of C.arborea root bark extract on globulin of alloxan-induced diabetic rats————————————————– 142
4.22 Effect of chronic administration of C.arborea root bark extract on albumin:globulin ratio of alloxan-induced diabetic rats——————————— 142
4.23 Effect of chronic administration of C.arborea root bark extract on blood urea nitrogen of alloxan-induced diabetic rats ———————————— 142
4.24 Effect of chronic administration of C.arborea root bark extract on creatinine of alloxan-induced diabetic rats———————————————— 146
4.25 Effect of chronic administration of C.arborea root bark extract on total bilirubin of alloxan-induced diabetic rats ——————————————- 146
4.26 Effect of chronic administration of C.arborea root bark extract on conjugated bilirubin of alloxan-induced diabetic rats ———————————— 146
4.27 Effect of chronic administration of C.arborea root bark extract on unconjugated bilirubin of alloxan-induced diabetic rats ——————————— 150
4.28 Effect of chronic administration of C.arborea root bark extract on AST:ALT ratio of alloxan-induced diabetic rats —————————————- 150
4.29 Effect of chronic administration of C.arborea root bark extract on BUN:Creatinine ratio of alloxan-induced diabetic rats———————————– 150
4.30 Effect of chronic administration of C.arborea root bark extract on red blood cell count of alloxan-induced diabetic rats———————————— 154
4.31 Effect of chronic administration of C.arborea root bark extract on total haemoglobin Concentration of alloxan-induced diabetic rats——————— 154
4.32 Effect of chronic administration of C.arborea root bark extract on packed cell volume of alloxan-induced diabetic rats ————————————- 154
4.33 Effect of chronic administration of C.arborea root bark extract on mean corpuscular volume of alloxan-induced diabetic rats—————————– 158
4.34 Effect of chronic administration of C.arborea root bark extract
on mean corpuscular haemoglobin concentration of alloxan-induced diabetic rats——- 158
4.35 Effect of chronic administration of C.arborea root bark extract on mean corpuscular haemoglobin of alloxan-induced diabetic rats ————————– 158
4.36 Effect of chronic administration of C.arborea root bark extract on total white blood cell count of alloxan-induced diabetic rats—————————- 158
4.37 Effect of chronic administration of C.arborea root bark extract on total lymphocyte count of alloxan-induced diabetic rats——————————— 163
4.38 Effect of chronic administration of C.arborea root bark extract on neutrophil count of alloxan-induced diabetic rats—————————————— 163
4.39 Effect of chronic administration of C.arborea root bark extract on total basophil of alloxan-induced diabetic rats ——————————————- 163
4.40 Effect of chronic administration of C.arborea root bark extract on eosinophil of alloxan-induced diabetic rats———————————————— 163
4.41 Effect of chronic administration of C.arborea root bark extract on total monocyte of alloxan-induced diabetic rats—————————————— 163
4.42 Effect of chronic administration of C.arborea root bark extract on malondialdehyde levels of alloxan-induced diabetic rats ——————————– 169
4.43 Effect of chronic administration of C.arborea root bark extract on superoxide dismutase activities of alloxan-induced diabetic rats ———————– 169
4.44 Effect of chronic administration of C.arborea root bark extract on reduced glutathione values of alloxan-induced diabetic rats—————————– 169
4.45 Effect of chronic administration of C.arborea root bark extract on catalase activities in alloxan-induced diabetic rats—————————————- 173
4.46 Effect of chronic administration of C.arborea root bark extract on weekly weight of alloxan-induced diabetic rats —————————————— 173
4.47 Pancreas of normal control rat showing well populated islet cells ———————— 176
4.48 Pancreas of diabetic untreated rat showing severe depopulation of islet cells with cytoplasmic vacuolations—————————————————————————– 176
4.49 Pancreas of diabetic rat treated with 62.5 mg/kg extract showing mild depopulation of islet cells —————————————————————————————————– 176
4.50 Pancreas of diabetic rat treated with 125 mg/kg extract showing well populated islet cells———————————————————————————————— 180
4.51 Pancreas of diabetic rat treated with 250 mg/kg extract showing relatively well populated islet cells———————————————————————————————— 180
4.52 Pancreas of diabetic rat treated with 2 mg/kg glibenclamide showing fully populated islet cells —————————————————————————————————– 180
4.53 Kidney of normal control rat showing normal glomerulus and renal tubules with normal epithelial cells—————————————————————————————— 184
4.54 Kidney of diabetic untreated rat showing glomerulonephritis and necrosis of the tubular epithelial cells with mononuclear cells infiltration ———————————————— 184
4.55 Kidney of diabetic rat treated with 62.5 mg/kg extract showing glomerulonephritis and necrosis of the tubular epithelial cells with mononuclear cells infiltration——————— 184
4.56 Kidney of diabetic rat treated with 125 mg/kg extract showing normal tubular epithelial cells —————————————————————————————————– 188
4.57 Kidney of diabetic rat treated with 250 mg/kg extract showing relatively normal tubular epithelial cells—————————————————————————————— 188
4.58 Kidney of diabetic rat treated with 2 mg/kg glibenclamide showing tubular epithelial cells without any observable lesion———————————————————————— 188
4.59 Liver of normal control rat showing central vein and normal arrangement of hepatocytes in cords—————————————————————————————————– 192
4.60 Liver of diabetic untreated rat showing severe degeneration and necrosis of hepatocytes and mononuclear cells infilteration———————————————————————– 192
4.61 Liver of diabetic rat treated with 62.5 mg/kg of extract showing mild mononuclear cells infiltration ———————————————————————————————- 192
4.62 Liver of diabetic rat treated with 125 mg/kg of extract showing mild periportal degeneration of hepatocytes—————————————————————————————— 196
4.63 Liver of diabetic rat treated with 250 mg/kg of extract showing no obvious lesions —- 196
4.64 Liver of diabetic rat treated with 2 mg/kg glibenclamide showing central vein and normal arrangement of hepatocytes in cords —————————————————————- 196
4.65 Heart of normal control rat showing normal arrangement of the myocytes————— 200
4.66 Heart of diabetic untreated rat showing degeneration of myocytes———————— 200
4.67 Heart of diabetic rat treated with 62.5 mg/kg extract showing normal muscle cells—– 200
4.68 Heart of diabetic rat treated with 125 mg/kg extract showing normal myocytes——— 200
4.69 Heart of diabetic rat treated with 250 mg/kg extract showing myocytes with no obvious lesion—————————————————————————————————- 205
4.70 Heart of diabetic rat treated with 2 mg/kg glibenclamide showing normal muscle cells-205
4.71 Chromatogram of active fraction 2:1———————————————————- 205
H proton Nuclear Magnetic Resonance (NMR) of the active compound —————- 209
4.73 13Carbon Nuclear Magnetic Resonance of the active compound————————— 209
4.74 Structure of the active compound————————————————————– 209

CHAPTER FIVE
5.0 Discussion and Conclusion ———————————————————————- 213
5.1 Discussion—————————————————————————————— 213
5.2 Conclusion —————————————————————————————– 226
REFERENCES ————————————————————————————— 228
APPENDIX————————————————————————————————-264

 

CHAPTER ONE INTRODUCTION

Diabetes is a complex and a multifarious group of metabolic disorders that disturbs the metabolism of carbohydrates, fats and protein (Kahn and Shechter, 1991; Bliss, 2000). It is characterized by increased fasting and postprandial blood glucose levels. Diabetes mellitus is a group of metabolic disorder resulting from defects in insulin secretion or reduced sensitivity of the tissues to insulin action or both (Lanza et al., 2001).

It is a disease characterized by inability to regulate blood glucose as a result of relative or absolute deficiency in insulin. This results to hyperglycemia often accompanied by glycosuria, polydipsia and polyuria (Celik et al.,2002) Besides hyperglycaemia, several other factors like hyperlipidaemia and enhanced  oxidative stress play a major role in diabetes pathogenesis.

The disease is progressive and is associated with high risk of complication (Dewanjee et al., 2008). It is one of the most common endocrine diseases and has a prevalence rate varying from 1- 50% (King and Rewers, 1993).

The term “Diabetes Mellitus” is derived from the Greek words dia (through), bainein (to go) and diabetes literally means pass through. The disease causes loss of weight as if the body mass is passed through the urine. Although it was known for centuries that the urine of patients with diabetes was sweet, it was not until 1674 that the physician named Willis coined the term Diabetes mellitus (from the Greek word for honey) (Vasudevan and Kumari, 2005).

Although many types of Diabetes mellitus exist (Tierney et al, 2002), it has been broadly classified into two by World Health Organization (WHO, 1980). Type I diabetes mellitus – insulin dependent Diabetes mellitus and type 2 Diabetes mellitus-Non insulin dependent Diabetes mellitus. Type 1 Diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islet of langerhans in the pancreas, leading to insulin deficiency.

This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, in which beta cell loss is a T-cell-mediated auto immune attack (Rother, 2007) Type 2 Diabetes mellitus is characterized by insulin resistance which may be combined with relatively reduced insulin secretion (Shoback, 2011).

Type 2 diabetes is the most common type. Other forms of diabetes that have been described include Gestational diabetes mellitus, type 3 diabetes mellitus (Alzeibers disease) and non specific types (Shoback, 2011). Gestational Diabetes mellitus (GDM) is a third major category of diabetes. It occurs in at least 5 to 14 percent of pregnancies.

It may improve or disappear after delivery (Cousens, 2008). Alzheimer’s disease has a strong connection with diabetes, obesity and heart disease. It is such strong connection that Alzheimer’s is being referred to by some scientists as type 3 diabetes (Rivera et al., 2005).

Alzeheimer’s disease is a chronic neuro-degenerative disease that usually starts slowly and gets worse over time (Burns and Lliffe, 2009). The most common early symptom is difficulty in remembering recent events (Short term memory loss) (Burns  and LLiffe, 2009). Mental and physical exercise and avoiding obesity may decrease the risk of Alzheimers disease (Ballard et al., 2011).

Other specific types of Diabetes mellitus include Latent autoimmune diabetes of adults (LADA) which is a condition in which type 1 Diabetes mellitus develops in adults. Adults with LADA are frequently initially misdiagnosed as having type 2 DM based on age rather than etiology.

Genetic mutations (autosomal or mitochrondrial) can lead to defects in beta cell function. Any disease that can cause extensive damage to the pancreas may lead to diabetes (for example chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells (WHO, 1999).

The incidence of Diabetes mellitus in dogs and cats has been noted. Middle to older dogs and cats are mainly affected. Females are affected twice as often as males and the incidence appears to be increased in certain small breeds such as chow chow, Alashan Malamute, poorly (Kahn, 2005).

Diabetes mellitus affects 1 in 400 (0.25%) cats through recent studies. Mc Cann et al., (2007) noted that it is becoming more common lately in cats. The prevalence of diabetes mellitus in world population is increasing in epidemic proportion. In 1995, it was estimated that around 135 million people were affected by this condition and it was expected to affect 200 million by the year 2015 (King et al., 1998).

The World Health Organization warns that deaths due to diabetes will increase globally by as much as 80 percent in some regions over the next 10 years (WHO, 2005).

Common clinical signs of diabetes in dogs include polydipsia, polyuria, polyphagia with weight loss, bilateral cataract and weakness (Kahn, 2005). In cats the back legs may become weak and the gait may become stilted or wobbly consequent upon peripheral neuropathy.

Untreated, the condition leads to increasingly weak legs in cats and eventually mal-nutrition, ketoacidosis and or dehydration and death but prompt effective treatment can lead to diabetic remission (Rand and Marshal, 2005). There are two forms of complications-acute and chronic complications. Diabetic Ketoacidosis (DKA) is one of the acute complications.

Elevated levels of ketone bodies in the blood decrease the blood pH leading to DKA with classical signs of abdominal pains, lethargy, coma, hypotension, shock and death. Urine analysis will reveal significant levels of Ketone bodies (which appear in the urine after exceeding its renal threshold) (Aiello, 1998).

Another acute complication is hyperglycemic hypoosmolar state in which water will osmotically be withdrawn from the cells of a patient with very high blood sugar level, into the blood causing dehydration and increase in blood osmolarlity (Meyes, 2000).

Respiratory infection is another acute complication. The immune response is impaired in individuals with diabetes mellitus. Cellular studies have shown that hyperglycemia both reduces the function of immune cells and increases inflammation.

The vascular effects of diabetes also tend to alter lung function which leads to an increase in susceptibility to respiratory infections such as pneumonia and influenza among individuals with diabetes. Several studies show that diabetes is associated with slower recovery from respiratory infection (Ahmed et al., 2008).

All forms of diabetes increase the risk of long term complications. The major long term complications are relative to blood vessel damage (Boussageon et al., 2011). The damage to small blood vessels leads to microangiopathy which has been incriminated in other chronic complications such as diabetic retinopathy, diabetic neuropathy, diabetic nephropathy and diabetic cardiomyopathy, while damage to the large vessels (Macrovascular disease) is sequel to cardiovascular disease such as coronary artery disease, and diabetic myonecrosis (Muscle wasting) (Aristides et al., 2007).

Another chronic complication is diabetic encephalopathy in which there is increased cognitive decline and the risk of dementia observed in  diabetics. Various mechanisms are proposed including alterations to vascular supply of the brain and the interaction of insulin with the brain itself (Gispen and Biessels, 2000).

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