Acase with Maturity onset diabetes of young falsy diagnosed as type 1 diabetes mellitus , Mody is a rare type of diabetes due to autosomal dominant gene mutation, occurs in young age beloww 25 years old, usually mild hypoglycemia and no ketosis

1. Atypical Diabetes:
Case Study by
Mohammad G. Khalifa (MSc.)
Assisst. Lecturer of Internal Medicine ,
Diabetes and Endocrinology
Faculty of Medicine , Zagazig University
(12 nd Feb., 2020)

2. George M.,15-years-old male
patient presents to Diabetes
and Endocrinology outpatient
clinic to establish diabetes care
and revise his diagnosis.
he was diagnosed with T1DM
6 ms ago due to : polyuria ,
polyphagia . Polydepsia ,
headache , weight loss and
a FBS 140 mgldl.

3. He was asked about range of
his RBS which was ranging
around 200 mg/dl .
blood ketones 0.3 mmol/dl(-ve).
BMI 21 kg/m2 .( Non obese).
He was treated with SC insulin
Glargine 4-5 units at bed time
and rapid acting analogue after
meals if needed !.

4. He is followed up by
multidisciplinary diabetes
team for 3 years, during
this period his HBA1C 6.4 %
to 6.1 % , RBS from 90 to 202
mg/dl

6. • Many investigstions were done
which all came back normal
including:
- Thyroid function tests,
- GAD antibodies and IA-2
antibodies,
- C- peptide level ,
- lipid profile.
INVESTIGTIONS:

7. •Question 1.
What type of diabetes does he
most likely have?
• Type 1 diabetes
• Type 2 diabetes
• Latent autoimmune diabetes of
the adult (LADA).
• Maturity Onset Diabetes of
Young( Mody).
• Secondary diabetes.

8. •Question 1.
What type of diabetes does he
most likely have?
• Type 1 diabetes
• Type 2 diabetes
• Latent autoimmune diabetes of
the adult (LADA).
• Maturity Onset Diabetes of
Young( Mody).
• Secondary diabetes.

10. • Question 2.
What laboratory tests would
you like to order to confirm his
diabetes type?
• (Choose all options that apply)
1- Oral glucose tolerance test.
2- C-peptide coupled with a glucose test.
3- GAD and islet cell autoantibodies.
4- Lipid panel.

11. • Question 2.
What laboratory tests would
you like to order to confirm his
diabetes type?
• (Choose all options that apply)
1- Oral glucose tolerance test.
2- C-peptide coupled with a glucose test.
3- GAD and islet cell autoantibodies.
4- Lipid panel.

12. • Consequently genetic testing
was done later which found that
he Is heterogenous for HNF1α
mutation , this confirmed the
diagnosis of MODY 3

13. • This case has a number of
unique features. The patient was
diagnosed with DM at a young
age( 15 ys), but not while in
acute hyperglycemic crisis, and
is not overweight or obese. he
has no personal or family history
of autoimmunity, but had a
strong family history of diabetes
diagnosed as a young adult.
CASE DISCUSSION:

14. The best laboratory tests to determine
what type of diabetes the patient has
include a measure of endogenous insulin
production (C-peptide coupled with a
glucose test) and a measure of diabetes-
related autoimmunity (glutamic acid
decarboxylase [GAD] and islet cell
autoantibodies).
The C-peptide test informs us if his pancreatic
beta cells are working normally and the islet
cell autoantibodies help to determine whether
this is type 1 diabetes or not.
CASE DISCUSSION:

15. • The patient’s comprehensive metabolic
profile was mostly normal, other than a
high glucose of 220 mg/dL. His lipids
were: Total cholesterol 168 mg/dL, high-
density lipoprotein cholesterol 68
mg/dL, low-density lipoprotein
cholesterol 90 mg/dL, and triglycerides
82 mg/dL.
C-peptide was normal, despite a
glucose of 220 mg/dL.
Both his GAD and islet cell
autoantibodies were negative.
CASE DISCUSSION:

16. • A few things should jump out at your
mind on reviewing this case:
1- The patient had a strong family
history of diabetes (this really reduces
the likelihood of this being type 1 diabetes).
2- There was evidence that he still
makes insulin and no evidence of
autoantibodies (this too makes type 1
diabetes less likely).
3- His lipid panel was normal and he
isn’t obese (This makes this case less
likely to be type 2 diabetes).
CASE DISCUSSION:

17. • This young male likely has (MODY),
known as maturity-onset diabetes
of youth.
MODY is a collection of autosomal
dominant genetic conditions that
lead to hyperglycemia and is
typically present at a relatively
young age (ADA,2020).
CASE DISCUSSION:

18. • ADA CLASSIFICATION of DM:
Diabetes can be classified into the following general categories:
1. Type 1 diabetes (due to autoimmuneb-cell destruction,
usually leading to absolute insulin deficiency).
2. Type 2 diabetes (due to a progressive loss of
adequate b-cell insulin secretion frequently on the
background of insulin resistance)
3. GDM(diabetes diagnosed in the second or third trimester of
pregnancy that was not clearly overt diabetes prior to gestation)
.
4. Specific types of diabetes due to other causes, e.g.,
monogenic diabetes syndromes (such as neonatal
diabetes and maturity-onset diabetes of the young(MODY),
diseases of the exocrine pancreas (such as cystic fibrosis and
pancreatitis), and drug- or chemical-induced diabetes (such as
with glucocorticoid use, in the treatment of HIV/AIDS, or after
organ transplantation) (ADA,2020).

20. MODY is frequently characterized by onset of
hyperglycemia at an early age (classically
before age 25 years, although diagnosis may
occur at older ages).
MODY is characterized by impaired insulin
secretion with minimal or no defects in insulin
action (in the absence of coexistent obesity).
It is inherited in an autosomal dominant
pattern .
with abnormalities in at least 13 genes on different chromosomes
identified to date.
The most commonly reported forms are GCK-MODY (MODY2),
HNF1AMODY (MODY3), and HNF4A-MODY (MODY1)
(ADA,2020).

30. DIAGNOSIS:

32. • Diagnosis of MODY:
• A diagnosis of one of the three most
• common forms of MODY, including
GCKMODY, HNF1A-MODY, and HNF4A-
MODY, allows for more cost-effective
therapy: (no therapy for GCK-MODY;
sulfonylureas as first-line therapy for
HNF1A-MODY andHNF4A-MODY).
Additionally, diagnosis can lead to
identification of other affected family
members. Genetic screening is
increasingly available and cost-
effective (ADA,2020).

33. A diagnosis of MODY should be
considered in individuals who have
atypical diabetes and multiple
family members with DM not
characteristic of type 1 or type 2
diabetes (ADA,2020).

34. • In most cases, the presence of
autoantibodies for type 1 diabetes
precludes further testing for
monogenic diabetes,
but the presence of autoantibodies
in patients with monogenic
diabetes has been reported !.
Individuals in whom monogenic
diabetes is suspected should be
referred to a specialist for further
evaluation if available. (ADA,2020).

35. • It is critical to correctly diagnose one of
the monogenic forms of diabetes ,
because these patients may be
incorrectly diagnosed with type 1 or
type 2 diabetes, leading to suboptimal,
even potentially harmful, treatment
regimens and delays in diagnosing other
family members (ADA,2020).
The correct diagnosis is especially
critical for those with GCKMODY
mutations where multiple studies have
shown that no complications ensue in
the absence of glucose-lowering therapy
(ADA,2020).

36. QUESTION3

37. QUESTION3

38. • For individuals with MODY, the treatment
implications are considerable and
warrant genetic testing .
Clinically, patients with GCK-MODY
exhibit mild, stable, fasting
hyperglycemia and do not require
antihyperglycemic therapy except
sometimes during pregnancy.
• Patients with HNF1A- or HNF4A-MODY
usually respond well to low doses of
sulfonylureas, which are considered first-
line therapy (ADA,2020).

39. MANAGEMEN
T:

41. • Sulfonylureas bind to and close ATP-sensitive
K+ (KATP) channels on the cell membrane of
pancreatic beta cells, which depolarizes the
cell by preventing potassium from exiting.
This depolarization opens voltage-gated Ca2+
channels. The rise in intracellular calcium
leads to increased fusion of insulin granulae
with the cell membrane, and therefore
increased secretion of mature insulin.
• There is some evidence that sulfonylureas also
sensitize β-cells to glucose, that they limit
glucose production in the liver, that they
decrease lipolysis (breakdown and release of
fatty acids by adipose tissue) and decrease
clearance of insulin by the liver.

43. • His brother Aldo asked for
predicitve testing for MODY.
PREDICTIVE TESTING FOR MODY

44. QUESTION : 4

45. QUESTION : 4

46. • Genetic counseling is
recommended to ensure that
affected individuals understand
the patterns of inheritance and
the importance of a correct
diagnosis (ADA,2020).
The diagnosis of monogenic
diabetes should be considered in
children and adults diagnosed
with diabetes in early adulthood
with the following findings:

47. - Diabetes diagnosed within the first
6months of life .
- Diabetes without typical features of type
1 or type 2 diabetes (negative diabetes-
associated autoantibodies,nonobese,
lacking other metabolic features especially
with strong family history of diabetes).
- Stable, mild fasting hyperglycemia (100–
150 mg/dL [5.5–8.5 mmol/L]), stable A1C
between 5.6 and 7.6% (between 38 and 60
mmol/mol), especially if non obese
(ADA,2020).

48. PREDICTIVE TESTING FOR MODY

49. PREDICTIVE TESTING FOR MODY

50. CONCLUSION
• It is important to consider monogenic
diabetes in young patients with non-
acute presentation of diabetes,
absence of beta-cell autoimmunity,
and no signs of insulin resistance.
Careful monitoring and rapid referral
for genetic testing can establish
optimal treatment and avoid insulin
use.