**2. Classifications of diabetic mellitus**

The terms type 1 and type 2 are used for classification based on aetiological factors. The terms insulin-dependent and non-insulin-dependent are used for classifying pathophysiological conditions of diabetes mellitus regardless of the aetiological factors. However, it has been noticed that failure to administer insulin in an insulin-dependent condition can lead to ketosis and with resultant life threatening condition. In the same vein patients whose conditions do not require insulin treatment for prevention of ketosis or for survival are known to require insulin for glycaemic control and such patients are considered to be in a non-insulin-dependent state [13].

### **2.1. Type 1 diabetes mellitus**

resulting in insulin resistance. The abnormalities of carbohydrate, fat and protein metabolism have also been shown to result in deficient action of insulin on target tissues resulting from

Insulin resistance was recently reported to be associated with obesity and type 2 diabetes[11]. Recent studies suggest that a complex interaction between inflammation, endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction and autophagy dysregulation play an important role in insulin resistance. The stress-activated c-Jun N-terminal kinase (JNK) has been increasingly recognized as a central mediator of insulin resistance [11] and suppres‐ sion of the JNK pathway has been shown to improve insulin resistance and glucose tolerance. Also, hyperhomocysteinemia (HHcy) was found to induce insulin resistance in adipose tissue

The terms type 1 and type 2 are used for classification based on aetiological factors. The terms insulin-dependent and non-insulin-dependent are used for classifying pathophysiological conditions of diabetes mellitus regardless of the aetiological factors. However, it has been noticed that failure to administer insulin in an insulin-dependent condition can lead to ketosis and with resultant life threatening condition. In the same vein patients whose conditions do not require insulin treatment for prevention of ketosis or for survival are known to require insulin for glycaemic control and such patients are considered to be in a non-insulin-dependent

insensitivity or lack of insulin [9-10].

96 Antioxidant-Antidiabetic Agents and Human Health

**Figure 1.** The structure of the pancreas which houses islets of Langerhans

via activation of JNK pathway [12].

state [13].

**2. Classifications of diabetic mellitus**

Type 1 diabetes mellitus is caused by insulin deficiency due to destruction of pancreatic β-cells principally via an autoimmune reaction that can be triggered by different factors [14]. It can also develop in association with certain hereditary factors, such as Human Leukocyte Antigen (HLA) alleles. Typically, destruction of pancreatic β-cells progresses to absolute deficiency in insulin. This condition develops rapidly in young people and has been found to occur in any age group [14]. Similarly, autoantibodies against islet anti‐ gens (islet-associated antibodies) have been shown to increase in the early phase of the disease. Hence, pancreatic β-cell destruction involves autoimmune mechanisms. There‐ fore, type 1 diabetes mellitus is also known as 'autoimmune' type 1 diabetes mellitus [14, 15-16].

### **2.2. Type 2 diabetes mellitus**

Type 2 diabetes mellitus is one of the most common diseases of the western world and is associated with cardiovascular disease [17]. Type 2 diabetes mellitus (formerly called NIDDM, type II or adult-onset) is characterized by insulin resistance in peripheral tissue and an insulin secretory defect of the beta cell. This is the most common form of diabetes mellitus and is highly associated with a family history of diabetes, old age, obesity and lack of exercise. It is more common in women, especially women with a history of gestational diabetes. Type 2 diabetes mellitus is characterized by derangement of carbohydrate, protein and fat metabolism [18]. Insulin resistance and hyperinsulinemia eventually lead to impaired glucose tolerance [19].

Defective beta cells become exhausted, further fuelling the cycle of glucose intolerance and hyperglycaemia. The aetiology of type 2 diabetes mellitus is multifactorial with evidence of genetic involvement [20-21]. Types of diabetes mellitus of various known aetiologies are grouped together to form the classification called "other specific types." This group includes persons with genetic defects of beta-cell function (this type of diabetes was formerly called MODY or maturity-onset diabetes in youth) or with defects of insulin action; persons with diseases of the exocrine pancreas, such as pancreatitis or cystic fibrosis; persons with dysfunc‐ tion associated with other endocrinopathies (e.g., acromegaly); and persons with pancreatic dysfunction caused by drugs, chemicals or infections. Diabetic cardiomyopathy (DCM) has also been extensively reported in type 2 diabetes mellitus [22-25]. DCM is recognized as asymptomatic progressing structural and functional remodelling in the heart of diabetics, in the absence of coronary atherosclerosis and hypertension. Diabetic cardiomyopathy is a fairly common cause of heart failure in the native population with type-2 diabetes mellitus and results in high morbidity and mortality [22]. Few of the classical symptoms of DCM include marked left ventricular (LV) systolic dysfunction, dysfunction of coronary microcirculation, in relation with glycaemic levels, insulin resistance, sympathetic overdrive, endothelial dysfunction, abnormalities of the angiotensin-renin system, and remodelling/hypertrophy, diastolic dysfunction and impairment of coronary flow reserve (CFR) may be associated in DM [22-24].
