Table of Contents
Introduction
Diabetes Mellitus is a disease in which pancreas will be unable to produce insulin in required amount. It is third largest disease after heart disease and cancer. 6% to 8% of the population is affected by diabetes. In diabetes insulin is produced in higher amount or in some cases it is not produced in required amount. So it will affect the different main organs of the body and cause of blindness, renal failure stroke and heart attack. Diabetic patients have higher urine excretion, because normal insulin concentration in plasma is 20-30 µu/ml which is not produced. According to the international Diabetes Federation ( IDF) 2015, Atlas has estimated 415 million people worldwide who are affected by diabetes. But this may increase to 642 million by 2040. Diagnostic criteria of diabetes is weight loss, thirst, polyuria, blurred vision and pereinal infection. And in this condition blood glucose level is exceed from 70-120 mg.
Diabetes mellitus is divided into two classes:
- Insulin-dependent diabetes mellitus (IDDM)
- Non-insulin dependent diabetes mellitus (NIDDM)
In diabetes the person feels fatigue, pain in body and sometimes due to high blood pressure headache.
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Type 1 Diabetes which is known as IDDM is usually occur in childhood at 20 years -25 and 10-20% population is affected by it. In this case pancreas fail to produce insulin so patient depend upon insulin injection.
If you have marker of diabetes which is located on chromosome 6 and its a HLA (human leukocyte antigen) complex. These complexes are responsible for type 1 diabetes. Other factors are viral infection in which different viruses attack on body and cause of disease. In family history if both parents have diabetes than there is higher chances of diabetes in their children.In second condition if father have diabetes with type 1 then their child develop diabetes is slightly higher than the mother. other is autoimmune conditions. In which body immune system is to turn against itself. In which some HLA complex produced Type 1 diabetes and its symptom of diabetes appear when 80-90% β-cell are destroyed. duration of symptoms are week. These patients may also have other autoimmune disease which are Graves’ disease, Hashimoto’s thyroiditis and Addison’s disease.
Type 2 Diabetes or NIDDM usually occurs in adults at the age of 40 or above and it is found 80-90% diabetes population. It is commonly occur in obese people. In this case insulin production is high. Factors which are responsible for type2 are genetic and environment.
Duration of symptoms are months to years. It is hereditary because genetics play an important role in Type 2 Diabetes. If father and mother have diabetes then it does not guaranteed to develop it, instead it means they have a greater chance of developing type 2 in their children.
In type 2 if mother has diabetes then in children it is greater chance to develop as compare to father. Today more than 120 genetic loci are associated with type 2 diabetes. Citation: (Lysenko v, et al.,2008)
Normal blood glucose level is 70-120 mg/dl in a normal person but in diabetic patient it will 120 mg/dl then we need to diagnose it and we diagnose it by doing a test which is known as oral glucose tolerance test (OGTT).One other form of diabetes is maturity onset diabetes of young (MODY).
Abnormalities at three genetic loci on different chromosomes have now been recognized. Most common form is linked with mutations on chromosome 12 in hepatic nuclear transcription factor referred to as HNF1 (54).Second form is associated with mutations in glucolanase gene on chromosome 7P.Third form is clinical with mutation in the HNF4” gene on chromosome 20q. Recently fourth variant has recently described mutation in another transcription factor gene IPF-1 which in its homozygous form leads to total production agenesis. Citation:( Second repot. Geneva :WHO, 1980,Technical Report Series 646.associated with T2D).
Literature
Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus. Abbrevations: KCNJ11: gene encoding potassium inward-rectifying channel subfamily J, member11.
Gestational diabetes mellitus shows a same physiological history as type 2 Diabetes. In this case beta cell show non-functional and resistance to insulin. The women who have GDM at high risk of type 2 Diabetes. It was first reported during pregnancy. GDM result when beta cell of pancreas fails to control the insulin resistance during pregnancy. So, GDM and type 2 Diabetes have same genetic susceptibility. Women with type 2 Diabetes have high chances to develop GDM.
There are different genes which are responsible for type 2 Diabetes. E23K polymorphism of the potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11) gene and increased for type 2 Diabetes. Variations in the calpain 10 (CAPN10) gene have also been associated with type 2 Diabetes. These have high chances of GDM (N. Shaat et al., 2005). By genotyping we can give its proof that GDM and type 2 Diabetes have similar genetic predisposition.
Cellular and molecular pathophysiology at A Glance
In type1 Diabetes there is high production of blood sugar level. Different environmental and genetic factors are playing an important role in the causes of type 1 Diabetes. In present, different loci are specified which are responsible for genetic factors of Diabetes1 type. But only few genes are described by mechanism. Type 1 Diabetes occur in young age. Type 1Diabetes is an auto immune disease and more common in males. In Europe many people are affected by type 1Diabetes. It’s causing factors are genetic and environment. The genetic region which is linked to type 1Diabetes is human leukocyte antigen (HLA) locus 4 and like this gene which associated with insulin production are also identified.
Physiological mechanism of type 1Diabetes is through activation of immune system against Beta cell antigen and initiation of demagogic responses. So due to inefficient regulation of Beta-cells chronic immunologic responses will occur which leads to destruction of beta-cells and cause of death of Beta-cell is due to the physiological mechanism which antigens and initiation of immune response against other beta-cells.
Environmental factors which playing an important role in type 1Diabetes mellitus.
- Gut micro biota reduction
- Obesity
- Gluten
- Toxins
- Lack of vitamins
- Viruses
Main organ which takes part in pathophysiology is pancreas, genome wide association studies and their meta-analysis identified almost 60 genes which cause of genetic susceptibility to type 1Diabetes. These genes are present in pancreatic beta cells which reflect autoimmune nature of disease. These genes are also highlighter in molecular mechanism of type 1Diabetes mellitus and by this we can identify the complications which occur in type 1Diabetes mellitus. There are two major classes of complication.
- Micro-vascular
- Macro-vascular
Which affect heart, limbs, nervous system, eyes and kidney. To Right side of body shows macro-vascular complication. The left side of body shows micro-vascular complication.
Macro-vascular complications of type 1 Diabetes mellitus
A group of large blood vessel disease occur in patients and cardiovascular disease in diabetic patients occur four times higher as compared to non-diabetic patients. The risk of hypertension in TIDM patients is 30% higher as compared to non-diabetic patients and other diseases such as coronary artery, cerebrovascular and peripheral vascular disease are also due to macro-vascular complications.
Micro-vascular complication of type 1Diabetes mellitus:
In this small vessel damage and cause neuropathy, nephropathy and retinopathy by different mechanism. Diabetic vascular complication is an excellent example that clarify role of genetic factors, environmental factors and their interaction in disease progression.
Familial aggregation and heritability of type 1 Diabetes mellitus
In worldwide type 1Diabetes is increasing by 3% per year. It occur in early age and rate of 6.4/100,000 for 0-9 year old Asian and pacific Islands. Bu in Taiwan was 5.6/1,000,000 from 0-14 years old. Human leukocyte antigen (HLA) has found as major genetic determinants for type 1Diabetes. Strongly found in Europe and East Asian populations. The families which have diabetes type 1 are at greater risk for chronic diseases.
In familial resemblance and heritability of type 1Diabetes phenotypic variance was 66.50% for genetic factors (heritability) and environmental factors were 10.86% and the non-environmental factors were 22.64%. The autoimmune disease which shows significant familial co-aggregation linked with type 1Diabetes are rheumatosus arthritis, sjogren’s syndrome and systematic lupus erthematosus. Other diseases are thyroid simple goiter, for non-toxic nodular goiter. So genetic factors are very strong which contribute to type 1Diabetes with a heritability of 66.5%.
