Life style Disorders:Diabetes

Presented By Lee-Ann Kara 551033

What is diabetes?

Diabetes is a chronic disease that arises when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces.

So what is insulin?Insulin is a hormone synthesized in significant quantities in beta cells in the pancreas. Insulin enables cells to take in glucose from the blood and use it for energy.

Why is diabetes a serious concern?Global overview:

•At present 2014, it is estimated 285 million people.•The diabetic population is expected to explode to 438 million by 2030.•Currently the age group most affected is 40 – 59 years.• By 2030 it is expected that the age group 60-79 years are most likely to be affected the most.

•The worlds largest diabetic population is in India. (estimated at 50.8 million)• 70% of diabetic cases exist in poorer countries (with low incomes).

Global Diabetes Epidemic (From 2000 to 2030 - in millions)Lifestyle disorders such as obesity are fuelling the incidence of diabetes on a global

scale.

Two main types of diabetes?

Type 1

Type 2

Causes of types 1 diabetes:

Genetic susceptibility

Autoimmune destruction of beta cells

Environmental factors

Viruses and Infections

Infant feeding practices

Causes of type 2 diabetes:

Genetic susceptibility

Obesity and Physical inactivity

Insulin resistance

Abnormal glucose production by the liver

Beta cell dysfunction

Major symptoms of Diabetes

•Excessive thirst and increased urination.

•Fatigue

•Weightloss

•Blurred vision

•Slow healing sores

•Tingling hands and feet

•Red swollen tender gums

TAKE YOUR BODY’S HINTS

SERIOUSLY!

Major symptoms of Diabetes

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Complications

•Eye complications •Foot complications •Skin complications•Heart problems•Hypertension •Mental health •Hearing loss •Gum disease•Neuropathy•Nephropathy•PAD (peripheral arterial disease)•Stroke•Erectile dysfunction•Infections•Healing of wounds

Controlling Diabetes: Treatment

•All types of diabetes are treatable.

•Diabetes type 1 lasts a lifetime, there is no known cure.

•Type 2 usually lasts a lifetime, however, some people have managed to get

rid of their symptoms without medication, through a combination of exercise,

diet and body weight control.

•Patients with type 1 are treated with regular insulin injections, as well as a special

diet and exercise.

•Patients with Type 2 diabetes are usually treated with tablets, exercise and a special

diet, but sometimes insulin injections are also required.

If diabetes is not adequately controlled the patient has a significantly higher risk of developing complications!

Molecular action of insulin drugs

Insulin action in the cell. Insulin exerts multiple effects in the cell. Insulin action is mediated by the binding of insulin to its receptor, and thesubsequent phosphorylation of the receptor and other substrates by the receptor tyrosine kinase.

Prevention

Scientists discover new causes of diabetes

This article provides further insights on how the insulin-producing beta cells are formed in the pancreas.

Discovered that mutations in two specific genes which are important for development of the pancreas can cause the disease

These findings increase the number of known genetic causes of neonatal diabetes to 20

Aim:To perform a comprehensive search for recessive mutations in genes encoding transcription factors known to be critical for pancreatic development in mice in a large collection of PNDM patients born to consanguineous parents.

Tested mutations in homozygous regions encompassing known transcription factor genes independently of the clinical features to avoid the possible bias introduced when clinical features guide candidate gene testing.

Study used a combination of homozygosity analysis and sanger sequencing in 37 consanguineous patients with permenant neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development

Experimental procedures

CohortExclusion of

Nontranscription factor mutations in

PDNM

Detecting mutations of pancreatic

transcription factor genes

Genome- wide SNP analysis to

localize etiological gene

by linkage

Sequencing of pancreatic

transcription factor genes

Patient phenotype assessment

Results106 out of 121 patients with known genetic etiology had homozygous mutations.This confirms that neonatal diabetes in the offspring of consanguineous families is usually recessive.Nonsense homozygous NKX2-2 mutations were identified in 3 patients from two families.These mutations are pathogenic.All 3 patients were found to have severe defects in insulin secretion and show normal exocrine function.This has been show to be similar to mice that are homozygous for a targeted disruption of Nkx2-2 and die after birth due to severe hypergylcemia. They also have normal exocrine function however but lack beta cells.Patients found with NKX2-2 mutations were found to have severe developemental delay, thus affecting motor and intellectual function. Other features are cortical blindness and hearing impairment.This is consistant as the same neurological features have been seenin the Nkx2-2 knockout mouse, with Nkx2-2 being important for hindbrain development, ventral neuronal patterning and oligodendrocyte differentiation.

Results

•Two patients were found to have homozygous missense mutations in MNX1.•p.F248L and p.F272L•Homeodomain

Both patients in this study showed severe intrauterine growth retardation and have been diagnosed with diabetes in infancy. Showing no evidence of exocrine pancreatic dysfunction.A similar scenario was seen in Mnx1 null mice, where these mice are much smaller as compared to normal size mice, have reduced number of beta cells but a normal exocrine function.Patient 1 was found to have extrapancreatic developmental features which includes growth retardation, difficulties swallowing, severe constipation, and neurological complications.This patient died at 10 months due to respiratory failure.Mnx1 null mice are difficult to study since they die at birth due to respiratory paralysis.Patient 2 didn’t show any extrapancreatic developmental features.

Further studies are required to investigate the variability in phenotype between the two patients.

LimitationsThe minimum prevalence of transcription factor mutations in our cohort of patients with consanguineous PDNM was 7.5 % but the true prevalence may be slightly higher since heterozygous or compound heterozygous mutations would have been missed as a result of the study design.Limited information on pancreatic development is provided since patients with the two mutations have severe developmental delay suggesting that in depth studies of pancreatic development and neurological function isnt possible.

Conclusion

Results confirm that the consequence of inactivation of pancreatic transcription factor genes in humans is similar to the phenotype observed in knockout mice.Mutations in NKX2-2 and MNX1 cause neonatal diabetes.Confirms a key role for NKX2-2 and MNX1 in human pancreatic development.This study validates the use of knockout mice for understanding beta cell development in humans.

Future prospects

•Parents will now have answers for their children with this rare

condition.

•This study will help scientists understand how the pancreas develops.

•Knowing the cause of diabetes will result in improved treatment.

•Will provide insight to people with future pregnancies.

•Knowing the which mutations of etiological genes are responsible for

diabetes, can potentially serve as a platform for future research and

create therapeutic drugs that can prevent these mutations from

occuring.

•However further research is needed

What causes diabetes?

Insulin is made in the pancreas, an organ located behind the stomach. The pancreas contains clusters of cells called islets. Beta cells within the islets make insulin and release it into the blood

If beta cells don’t produce enough insulin, or the body doesn’t respond to the insulin that is present, glucose builds up in the blood instead of being absorbed by cells in the body, leading to prediabetes or diabetes

In diabetes, the body’s cells are starved of energy despite high blood glucose levels.

However?No one is certain what starts the processes that cause diabetes, but scientists believe genes and environmental factors interact to cause diabetes in most cases.

Summary•Diabetes is a complex group of diseases with a variety of causes. Scientists believe genes

and environmental factors interact to cause diabetes in most cases.

•People with diabetes have high blood glucose, also called high blood sugar or

hyperglycemia. Diabetes develops when the body doesn’t make enough insulin or is not able

to use insulin effectively, or both.

•Insulin is a hormone made by beta cells in the pancreas. Insulin helps cells throughout the

body absorb and use glucose for energy. If the body does not produce enough insulin or

cannot use insulin effectively, glucose builds up in the blood instead of being absorbed by

cells in the body, and the body is starved of energy.

•The two main types of diabetes are type 1 diabetes and type 2 diabetes..

•Type 1 diabetes is caused by a lack of insulin due to the destruction of insulin-producing

beta cells. In type 1 diabetes—an autoimmune disease—the body’s immune system attacks

and destroys the beta cells.

•Type 2 diabetes develops when the body can no longer produce enough insulin to

compensate for the impaired ability to use insulin.