Acc Supervisor

Telah dibacakan 22 Desember 2015

Pimpinan Sidang

dr. Zuhrial Zubir, Sp.PD, KAI

CASE REPORT
Maturity Onset Diabetes of The Young Complicated with Gangrene Diabetic
Andry Syahreza, Dian Anindita, Melati Silvani Nasution, M. Aron Pase, Santi
Syafril, Dharma Lindarto
Endocrine, Metabolic & Diabetes Division, Internal Medicine Department
Medical Faculty University of Sumatera Utara / Adam Malik General Hospital
ABSTRACT
Maturity onset diabetes of the young (MODY) is a clinical heterogen
disease with a characteristic of non insulin dependent diabetes that were
diagnosed at age < 25 years with a dominant autosomal transmission and lack of
autoantibody. MODY is one of monogenic diabetes that often found in 2-5% of
diabetes patients. The characteristics of the patients were very hard to notice that
affect the pathogenesis. Genes that involved in development, function, regulation
and mutation of beta cells lead to minimal disruption of insulin sensitivity and
secretion of insulin. The mutation to hepatocyte nuclear factor-1-alpha (HNF1A),
glucokinase (GCK), HNF4A had been identified in few cases of MODY and
genes that have not been identified.1,2,3,4
We report a case of 35 years old female came to HAM central government
hospital complained ulcers on her left foot. Initially, they were bubbles that
contained fluids and then ruptured, spread to fingers and ankle. These were
happened 1 month ago prior entering the hospital. The ulcers on the fingers then
started to blackened and spread to all of the left foot. Pain, smelly pus were found.
Fever was found 2 weeks before entering the hospital, but it was not too high and
increased slowly. The fever were intermittent and came down using drugs. History
of frequent drinking, eating and nocturnal dysuria were found. History of
hyperglicemia was found since age 17 years with glucose level above 200 mg/dL.
Her grandfather (from her father) also had a history of hyperglicemia. There were
no history of giving birth above 4 kg and also obesity since young. From the
physical examination, the haemodynamic were stable, body weight was 56 kg,
160 cm in height, and it was a normoweight body mass index. Anemic
conjunctiva palpebra inferior was found, and there were no acantosis nigricans,
normal thorax examination, and no striae on the abdomen. Ulcers were found on
the left foot, pus and blood were also found along with necrotic tissues. The
pulsation of the vascular were weaker at the left leg. PEDIS Score criteria was 10.
The laboratory examination showed anemia (Hb: 8,4 g%), leukocytosis
(15.510/mm3), high blood glucose (234,2 mg/dL), high fasting blood glucose (324
mg/dL), high 2 hours post prandial glucose (287 mg/dL), normal lipid profiles
(total cholesterol: 91 mg/dL, Triglyseride: 95 mg/dL, HDL: 24 mg/dL, LDL: 41
mg/dL), low fasting C-Peptide (0,25 ng/dL, normal value was 0,9-7,1 ng/dL) and
from the pus bacteria culture found Proteus mirabilis that was sensitive to
Meropenem, Amikacin and Erfapenem. The patient then got Meropenem injection
1 gram/8 hours/i.v, Metronidazole drips 500 mg/8 hours, Humulin R injection 8-88 International Unit/ h.a.c/s.c, Humulin N injection 10 International Unit at
night. Her left foot was also amputated.
Keywords: MODY, Gangrene Diabetic

I. INTRODUCTION
Maturity Onset Diabetes of the Young (MODY) is a term which used first time in
1970th to described an abnormality of diabetes that was differrent from type 1
diabetes (insulin dependent) and type 2 diabetes (non insulin dependent). The
basic of genetic molecular of MODY had been known since 1990, indicated the
genetic mutation that lead to diabetes especially to its effect to beta cells of
pancreas.1
MODY is a group of monogenic abnormality that were heterogenous
marked by non dependent insulin diabetes in juvenile (before age 25). This
abnormality was hereditarily autosomal dominant. Genes that get involved in this
were an important gene for growth, functionality, the regulation of beta cells and
can make a disturbance in the regulation of glucose and insulin secretion.2,3
MODY is seldomly detected until adult. It is found around 1-5% in all
diabetes patients in United States. Patients that only have a slight symptom or
without any diabetic or hyperglicemic symptom often found in a routine check up
and generally the patients arent overweight and dont have any other risk factor
for type-2 diabetes, e.g high blood pressure or hyperlipidemia. MODY can be
given oral anti diabetes and it is not like type-1 insulin that always need insulin.
The medications varies rely on genetic mutations that cause MODY.4
II. CASE REPORT
Female, 35 years, came to HAM central government hospital complained
ulcers on her left foot. Initially, they were bubbles that contained fluids and then
ruptured, spread to fingers and ankle. These were happened 1 month ago prior
entering the hospital. The ulcers on the fingers then started to blackened and
spread to all of the left foot. Pain, smelly pus were found. Fever was found 2
weeks before entering the hospital, but it was not too high and increased slowly.
The fever were intermittent and came down using drugs. History of frequent
drinking, eating and nocturnal dysuria were found. History of hyperglicemia was
found since age 17 years with glucose level above 200 mg/dL and she had taken
oral anti diabetic medicine, but occasionally and stopped after sometimes. Her

grandfather (from her father) also had a history of hyperglicemia. There were no
history of giving birth above 4 kg and also obesity since young.
From the physical examination, the haemodynamic were stable, body
weight was 56 kg, 160 cm in height, and it was a normoweight body mass index.
Anemic conjunctiva palpebra inferior was found, and there were no acantosis
nigricans, normal thorax examination, and no striae on the abdomen. Ulcers were
found on the left foot, pus and blood were also found along with necrotic tissues.
The pulsation of the vascular were weaker at the left leg. PEDIS Score criteria
was 10.
The laboratory examination showed anemia (Hb: 8,4 g%), leukocytosis
(15.510/mm3), high blood glucose (234,2 mg/dL), high fasting blood glucose (324
mg/dL), high 2 hours post prandial glucose (287 mg/dL), normal lipid profiles
(total cholesterol: 91 mg/dL, Triglyseride: 95 mg/dL, HDL: 24 mg/dL, LDL: 41
mg/dL), low fasting C-Peptide (0,25 ng/dL, normal value was 0,9-7,1 ng/dL) and
from the pus bacteria culture found Proteus mirabilis that was sensitive to
Meropenem, Amikacin and Erfapenem.
The patient then got Meropenem injection 1 gram/8 hours/i.v,
Metronidazole drips 500 mg/8 hours, Humulin R injection 8-8-8 International
Unit/ h.a.c/s.c, Humulin N injection 10 International Unit at night. Her left foot
was also amputated.

III. Discussion
Monogenic Diabetes defined as diabetes that occur from mutation of single gene
which affects the function of beta cells. This mutation involve genes that encodes
transcription factor in development of beta cells, differentiation and survival; like
glucokinase enzyme (GCK) and carboxil ester lipase (CEL). Nenonatal diabetes
mellitus (NNDM) and MODY are 2 main types of monogenic diabetes that cause
dysfunction of beta cells. Another form of monogenic diabetes causes defects on
insulin function or insulin reseptor.5
A. Classification
Table 1. MODY subtype5

Tabel 2. Gen yang terlibat pada MODY dan fenotip klinisnya (Fajans et al, 2001)3

Table 2. Clinical Features of MODY5

Table 3. Relative Prevalence of MODY5

B. Diagnosis
MODY can be diagnosed by direct sequencer of genes (Sensitivity up to 100%).
However, this examination is very expensive up to $550 per gene and can only be
done in certain specialist center. The clinical finding of the patients with MODY
oftenly overlapped with type 1 or type 2 diabetes. MODY and type-1 diabetes
usually diagnosed on young people and insulin dependent, while MODY and type
2 diabetes usually dont need insulin injection, and still produced insulin years
after diagnosis and dont have any prove of beta cells autoimmunity.11

Table 4. Differences of type-1, type-2 DM and MODY6

Tattersall and Fajans in 1975 made a clinical criteria for diagnosis of MODY in
diabetic patients. They are as follows:5
1. Early onset diabetes (<25 years)
2. Early onset diabetes at least on 2 or 3 family members,
3. Dominant autosomal inheritage,
4. Non-dependent insulin (didnt need insulin even after 5 years after diagnosis).

There is also online probability counting methods that can be used to help
decide to predict MODY and when to check genetic examination. Its accessible at
http://www.diabetesgenes/org/content/mody-probability-calculator. This model
consider these parameters:6
-

Age at diagnosis

Sex

Insulin or oral hyperglicemic medication

Body Mass Index (BMI)

when insulin given

HbA1c level

History of family with diabetes

Current Age

C-peptide7
C-peptide is a peptide composed of 31 amino acids. It is released from the
pancreatic beta-cells during cleavage of insulin from proinsulin. It is mainly
excreted by the kidney, and its half-life is 3-4 times longer than that of insulin.
The insulin precursor, preproinsulin, is produced in the rough endoplasmic
reticulum of pancreatic beta-cells and is later cleaved to proinsulin and
transported to the Golgi apparatus, where is packed into secretory granules.
During maturation of this granules, proinsulin is cleaved into 3 peptide chains
insulin (2 chains, A and B) and C-peptide.
Although, historically, C-peptide was considered to have no biologic
activity; recent studies suggest that C-peptide may improve capillary blood flow
in the feet, decrease urinary albumin excretion, and improve nerve function in
individuals with type 1 diabetes.
Indications/Applications
C-peptide should be measured in the combination of insulin and proinsulin as part
of the workup for nondiabetic hypoglycemia to differentiate between insulindependent hypoglycemia (high C-peptide levels) versus insulin-independent
hypoglycemia (low C-peptide levels). For appropriate interpretation of these tests,

low serum blood glucose levels (< 55 mg/dL; preferably < 45 mg/dL) should be
documented in the same blood sample.
In combination with serum and/or urine sulfonylurea screening, C-peptide
testing can help differentiate between factitious hypoglycemia due to exogenous
insulin use (low C-peptide level, high insulin level) and sulfonylurea intoxication
(high C-peptide level, high insulin level).
C-peptide can also be used for the following:

To monitor pancreatic function after a pancreatic transplantation or

pancreatectomy.

To monitor beta-cell function in a patient with early-stage type 1 diabetes

mellitus who is receiving immunomodulatory therapy to slow disease
progression.

To differentiate between type 2 diabetes mellitus and latent autoimmune

diabetes of adults (LADA).
The reference range of C-peptide is 0.8-3.1 ng/mL (conventional units), or

0.26-1.03 nmol/L (SI).

C-peptide levels are elevated in the following:

Insulinoma

Sulfonylurea intoxication

Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS)

Insulin resistance state (eg, obesity , Cushing syndrome )

Chronic kidney disease

C-peptide levels are suppressed in the following:

Type 1 diabetes mellitus

Exogenous insulin injection (factitious)

Hypoglycemia due to insulin-like growth factor secreting tumor

Insulin-independent hypoglycemia

Diagram 1. Diagnostic Approach Diagram of Young Onset Diabetes.5

In this case, the patient has a history of hyperglicemia at age 17 and since
then, she take anti diabetic oral occasionally and stopped after sometimes,
but she didnt have any complications, no history of using insulin (means non

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insulin dependent), no history of metabolic syndrome (high blood pressure,

dyslipidemia, obesity) and also no history of giving birth >4 kg. She had a
grandfather that had a same history as her. We also checked fasting Cpeptide that shows a low level. This means that shes not a type-2 diabetes but
also not insulin dependent diabetes (type-1 diabetes). Its concluded that she
was a suspected MODY patients, but in Adam Malik hospital cannot check
the genes examination to have a 100% diagnosis.

IV. CONCLUSION
We reported a case of MODY complicated with Gangrene Diabeticum in a 35
years old woman based on clinical features and laboratory examinations. He was
given pharmacotherapy and amputated to prevent further infections.

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REFERENCES
1. Gardner DSL & Tai ES. Clinical features and treatment of maturity onset
diabetes of the young (MODY). Diabetes, Metabolic Syndrome and Obesity:
Targets and Therapy 2012; 5:101-108.
2. Naylor R & Philipson LH. Who should have genetic testing for maturity onset
diabetes of the young?. Clinical Endocrinology 2011; 75:422-426.
3. Fajans SS, Bell GI & Polonsky KS. Molecular Mechanisms and Clinical
Pathophysiology of Maturity Onset Diabetes of the Young. N Engl J Med 2001;
345(13):971-980.
4. National Institute of Diabetes and Digestive and Kidney Diseases. Monogenic
Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity Onset Diabetes of
the Young. U.S. Department of Health and Human Services. 2007. NIH
Publication No. 07-6141.
5. Nair VV, Chapla A, Arulappan N & Thomas N. Molecular diagnosis of
maturity onset diabetes of the young in India. Indian Journal of Endocrinology
and Metabolism 2013; 17(3):430-441.
6. Kavvoura FK & Owen KR. Maturity Onset Diabetes of the Young: Clinical
Characteristics, Diagnosis and Management. Ped Endocrinol Rev 2013;
10(2):234-242.

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7. Elhomsy,

G.

et

al.

2014.

C-Peptide.

Available

from:

http://emedicine.medscape.com/article/2087824-overview#showall. Accessed
12 Desember 2015.

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