Case study on MODY (Maturity onset diabetes of the young) – Taper down of the sulfonylurea doses

Manickavasagam*

Physician Assistant, Department of Medicine, Kauvery Hospital, Hosur, Tamil Nadu

*Correspondence

Abstract

Maturity-Onset Diabetes of the Young (MODY) is a rare hereditary form of diabetes caused by single-gene mutations affecting insulin production and secretion. It commonly develops before the age of 25 years and is often misdiagnosed as Type 1 or Type 2 diabetes because of overlapping clinical features. MODY is inherited in an autosomal dominant pattern and is associated with mutations in genes such as HNF1A, HNF4A, and GCK. Early and accurate diagnosis is important because the treatment and prognosis differ from other types of diabetes. Genetic testing plays a major role in confirming the diagnosis and guiding individualized management. Awareness about MODY helps in improving patient outcomes, preventing complications, and providing appropriate family screening and counseling.

Key words: Maturity-Onset Diabetes of the Young (MODY); Hyperglycemia

Introduction

Maturity-Onset Diabetes of the Young is a monogenic form of diabetes characterized by early onset hyperglycemia resulting from impaired pancreatic beta-cell function. Unlike Type 1 diabetes, MODY usually occurs without autoimmune destruction of beta cells, and unlike Type 2 diabetes, it is not commonly associated with obesity or insulin resistance. MODY accounts for approximately 1–5% of all diabetes cases, although many patients remain undiagnosed due to lack of awareness and similarities with other diabetes types. The condition is inherited in an autosomal dominant manner, meaning that affected individuals often have a strong family history of diabetes across multiple generations. Several subtypes of MODY have been identified based on the specific gene mutation involved. The most common forms include HNF1A-MODY, HNF4A-MODY, and GCK-MODY. Clinical presentation may vary from mild fasting hyperglycemia to progressive diabetes requiring pharmacological treatment.

Accurate diagnosis of MODY is essential because treatment strategies differ according to the subtype. Some patients respond well to oral sulfonylureas, while others may require only lifestyle modifications. Genetic counseling and screening of family members are also important aspects of management. Understanding the clinical and genetic features of MODY can help healthcare professionals provide early diagnosis, appropriate treatment, and better long-term outcomes for patients.

Diabetes Mellitus

Diabetes mellitus is a chronic metabolic disorder characterized by high blood sugar (Hyperglycemia) due to insufficient  insulin production in pancreas . There are 4 types of diabetes mellitus.

  • Type 1 diabetes mellitus
  • Type 2 diabetes mellitus
  • Gestational Diabetes mellitus
  • MODY (Maturity Onset of Diabetes of the Young )

Type 1 Diabetes mellitus: The immune system destroys insulin producing beta cells in the pancreas, leading to little or no insulin production

Type 2 Diabetes mellitus: The body’s cells become resistant to insulin and/or the pancreas fails to produce enough insulin to overcome this resistance.

Gestational Diabetes mellitus : High blood sugar develops during pregnancy

MODY

MODY (Maturity onset of Diabetes of the Young) that is a rare, inherited form of Diabetes caused by a single gene (HNF1B-MODY) mutation, typically diagnosed in adolescents or young adults under 25 years.

Common Subtypes

  • MODY 3 (HNF1A): The most common type. It is progressive but often responds well to low doses of oral medications like sulfonylureas.
  • MODY 2 (GCK): Usually causes mild, stable high blood sugar that typically does not require treatment or cause long-term complications.
  • MODY 1 (HNF4A) : Similar to MODY 3 and often treated with sulfonylureas; babies born to such mothers may have low blood sugar at birth.

Symptoms: Gradual rise to high blood sugar, Classic Diabetic symptoms (Frequent urination, polyuria, polydipsia, significant weight loss), fatigability, blurred vision, dry skin.

Diagnosis

  • Strong Family history of Diabetes ( Both parents may have diabetes)
  • Insulin C peptide level check test
  • C-Peptide Test: Measures residual insulin production; MODY patients usually have normal or elevated levels ( >0.6 ng/ml) unlike type 1 Diabetes mellitus
  • HbA1c, Urea, Creatinine, Electrolytes
  • Random blood sugar
  • Presenting complaints and history of symptoms

Treatment

  • Diet and Lifestyle: Fundamental for all types.
  • Oral medications (Sulfonylureas): Often highly effective for HNF1A and HNF4A-MODY.
  • Insulin: Often required for HNF1B-MODY and in later stages of other types.
  • None: GCK-MODY (MODY2) usually requires only monitoring.

Case Presentation

A 25-year-old gentleman came to OPD with the complaints of significant weight loss of 15 KG in 4 months (+), Poor appetite, and very extreme tiredness (+), polyuria (+), no complaints of URTI symptoms

Vitals

Height187 Cm
Weight76 kg
Pulse rate118 b/m
Blood pressure120/70 mmHg
Spo299%
Temp98.2 F
Random blood sugar449 mg/dl.
Family history Both parents and grandfather have Diabetes and hypertension.

Advice to do CBC, RFT, LFT, Electrolytes, HbA1c, Urine routine, and fasting lipid profile, fasting insulin C-Peptide level.

Lab Investigation reports

CBCHB- 17.0g/dl, TC- 11660, Platelet count- 277000 Lakhs /Cumm
RFTSerum urea – 21.1, Creatinine – 0.7
LFTTotal Bilirubin – 1.3, Direct Bilirubin - 0.3, Indirect Bilirubin -1.0 , SGOT – 21, SGPT – 20
HbA1c15.1 %
Urine routine Sugar- 3 present +, pus cells – 02 to 04, EP cells – 02 to 03, Urine Ketone 2 present (+).
Lipid profile (Fasting)Total CHOL -183mg/dl, TGL-146mg/dl, LDL-115mg/dl
Insulin C- peptide level (Fasting)1.93 ng/mL. (Normal range0.5 to 2.0 ng/ml)
Electrolytes Sodium Na+ - 139mmol/L , Potassium K+ - 4.4mmol/L, Chloride - 104mmol/L.

Treatment

Tab. GLYCOMET GP2(Long acting Metformin and Glimepiride) – 1-0-1 (Before food). Advice to do after 20 days home sugar monitoring chart given. Dietitian review for Diabetic diet.

Home sugar Monitoring chart

Key of Causes

Monogenic – Unlike Type 1 or type 2 diabetes, MODY is caused by a single gene mutation, not multiple genes

Autosomal dominant inheritance – Strong family history of diabetes (both parents, grandfather and grandmother)

Fasting C-Peptide level

He came for review after one month, Response to OHAs was satisfactory. Patient followed strict diet. Complained of gastritis and occasional loose stools, increase weight gain, no other complaints.

Vitals

Weight81.3 kg
Blood pressure110/70 mmHg
Pulse rate108 b/m
Spo298 %
Temp98.2 °F
Lab InvestigationFBS - 93 mg/dL, PPBS - 133 mg/dL

Treatment given by (RX)

  • Taper down – Tab. GLYCOMET GP1 1- 0 -1
  • RABIGLAD DSR 20 mg 1-0-0 X 20 days
  • BIFILAC HP LOZENGES 1-0-1 X 20 days

Follow up 30 days with FBS, PPBS

After 30 days that patient to OPD. Symptomatically better, no other specific issues, sugar level controlled by OHAs, increase weight gain, good appetite.

Vitals checked

Weight87.3kg
Blood pressure120/70 mmHg
Pulse rate106 Bpm
Spo298 %
Temp98.2 °F
Lab InvestigationFBS - 95 mg/dL, PPBS - 130 mg/dL

Tapered OHAs : Rx given by GLYCOMET GP 0.5 OD dose 1-0-0

Diet and lifestyle Modification

  • Lifestyle modification regular walking and exercise, Yoga.
  • Avoid Alcohol and smoking.
  • Limited sugar level intake its make used to reduced weight gain.

Diet and food controlled

  • Prioritize complex carbohydrates and fiber: Choose whole grains (oats, brown rice, quinoa, barley) over refined flour products.
  • Choose healthy fat: use avocado, nuts , seeds, and oils like olive or canola for healthy
  • Avoid white sugar and added limited brown sugar level intake.
  • Sucrose that is quickly broken into glucose and fructose, causing rapid blood sugar spikes.

Complication of diabetes mellitus

  • Diabetic retinopathy
  • Diabetic neuropathy
  • Dyslipidaemia
  • DKA (Diabetic ketoacidosis)
  • Heart disease- CAD
  • Hypertension, Thyroid disorder
  • Infection (Phimosis , Balanoposthitis)

Prevention of Diabetes mellitus

  • Maintain Healthy weight
  • Regular physical activity
  • Eat healthy foods
  • Reduce sedentary time – (limit time spent sitting try taking short walks after meals)
  • Avoid alcohol, smoking and tobacco uses
  • Persons above 40 yrs of age advised to check Blood sugar every 6 months, Early diagnosis is important.
  • Symptoms like dysuria, polyuria, significant weight loss or weight gain, and chest pain should not be ignored. Health check-up is best way of prevention of Diabetes.

 

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