2. 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.

3. 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).

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

5. Two main types of diabetes?
Type 1
Type 2

6. Causes of types 1 diabetes:
Genetic susceptibility
Autoimmune destruction of beta cells
Environmental factors
Viruses and Infections
Infant feeding practices

7. Causes of type 2 diabetes:
Genetic susceptibility
Obesity and Physical inactivity
Insulin resistance
Abnormal glucose production by the liver
Beta cell dysfunction

8. 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!

9. Major symptoms of Diabetes
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10. 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

11. 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!

12. 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 the
subsequent phosphorylation of the receptor and other substrates by the receptor
tyrosine kinase.

13. Prevention

14. Scientists discover new causes of diabetes

15. 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
transcription factors known to be critical for pancreatic develo
a large collection of PNDM patients born to consanguineous p
Tested mutations in homozygous regions encompassing know
factor genes independently of the clinical features to avoid the
introduced when clinical features guide candidate gene testin

16. 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

17. Experimental procedures
Cohort
Exclusion 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

18. Results
106 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.

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

20. 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.

21. Limitations
The 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.

22. 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.

23. 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

24. 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.

25. 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.