CME INDIA Presentation by Dr. Ashish S. Dengra, MBBS, MD (medicine), Diploma diabetes (UK), C-diabetology (Mumbai), PGDHSC, Diabetology (Chennai), Fellow diabetes India, fellow RSSDI FIACM, FAMS. Director:  Mahi Diabetes, Thyroid Care and Research Centre, Jabalpur..

Indian Saga

Insulin Dilemma in Young Diabetics
  • Around 5th century BC, the famous Indian surgeon Sushruta, in his work Samhita, identified diabetes.
  • He used the term madhumeha (honey-like urine) and pointed out not only the sweet taste of the urine but also its sticky feeling to the touch and its ability to attract the ants (!).
  • Sushruta further mention that diabetes affects primarily the rich castes and is related to the excessive food consumption as the rice, cereals and sweets.

Diabetes has wide variations in presentation. Let us see the following cases and unlock the dilemma.

Case 1

  • A 10-year-old Girl presented with
  • 3Ps (Polyuria, polydipsia, polyphagia)
  • Abdominal pain.
  • Tiredness, weakness, loss of weight
  • Burning micturition
  • FBG- 209
  • PPBG- 378
  • HB1Ac- 10%
  • Past History: NIL Significant
  • Family History:  No history of DM in family
  • Weight-19.6 kg       Height -125 cm     BMI-12.5
  • No markers for Insulin Resistance
  • Dehydration present
  • Ketonuria++
  • Serum Beta hydroxy butyrate acid-) 0.34 mmmol/L (Markedly elevated)
  • TG-raised
  • Fasting C-Peptide: 0.2pmol/ml
  • [Normal more than 0.9 pmol/ml]
  • IMPRESSION: ABSENT BETA CELL FUNCTION
  • GAD 65 Antibody Test: 50 IU/ml
  • [Normal Value of lab Less than 8 IU/ml]
  • Result: POSITIVE

So, what is your Diagnosis?

TYPE 1 Diabetes

Treat with Insulin

Insulin Dilemma in Young Diabetics
Insulin Dilemma in Young Diabetics

Case 2

  • A 13-year-old girl, detected to have Diabetes since 8months, BMI 29kg/m2
  • She was informed that she has been Detected to have T1DM and was put on multiple doses Insulin Therapy.
  • However, BG remained uncontrolled. But she was asymptomatic.
  • FBG: 188mg% & PPBG- 269mg%, GHb- 9.2%
  • Strong family history of DM, Ketonuria: Absent

Insulin Dilemma in Young Diabetics

  • Height: 163cm, Weight: 73kg, BMI: 27.5kg/m2
  • HbA1c: 9.2%
  • S. Cholesterol 210mg%, TG: 280mg%
  • LFT, KFT, Hemogram, TSH Urine:  NAD
  • NO clinical evidence of micro/macroangiopathy
  • CXR, USG Abdomen, X-Ray Abdomen –NAD
  • Signs of Acanthosis Nigricans Positive on Neck

Which next investigation should we do?

Fasting C-Peptide: 1.3 pmol/ml

[Normal more than 0.9 pmol/ml]

IMPRESSION: Preserved beta cell function

GAD 65 Antibody Test: 4 IU/ml

[Normal Value of lab Less than 8 IU/ml]

Result: NEGATIVE

What is Your Diagnosis…?

  • Diagnosis: Early Onset Type 2 Diabetes: Suspect type 2 diabetes in any young patient who has…
  • Strong family history of diabetes
  • Signs of insulin resistance – Obesity, Acanthosis Nigricans
  • Fair to good beta cell reserve as measured by c-peptide
  • C-peptide assay and GAD antibody could help in distinguishing the various type of diabetes but are not essential for starting management

Case 3:

  • A 16-year-old girl, known case of diabetes since the age of 13years, on Basal bolus Insulin therapy presented with recurrent UTI & Vaginitis.
  • She had a strong family history of DM:
  • Mother
  • Maternal grandmother (Nani)
  • Maternal Aunts (Mousi)
  • Elder Sister

What should be your next step for diagnosis?

Pedigree Chart: Strong F/H of T2DM on Maternal side

Insulin Dilemma in Young Diabetics

  • On Examination:
  • Height 159cm, Weight: 52.4kg
  • BMI: 20.7kg/m2  
  • BP: 110/70mm of Hg 
  • Other Investigations: NAD
  • What Investigation will you advice?
  • Lipids: TC- 209mg%, TG- 132, LDL-C: 146mg%, HDL- 33mg%
  • KFT, LFT, TSH, Hemogram, CXR Normal, ECG: WNL
  • USG Abdomen: Normal
  • X-Ray Abdomen: No evidence of Pancreatic Calcification
  • Fasting C-Peptide: 1.4 pmol/ml
  • IMPRESSION: FAIRLY GOOD BETA CELL FUNCTION
  • CLINICAL DIAGNOSIS: MONOGENIC DM (MODY)

MODYEarly onset Type 2 diabetes
Non-obese Acanthosis nigricans uncommonObese /Overweight Acanthosis nigricans common
Three generation transmission with Only one parent affectedBoth the parents could be affected
Only insulin secretory defectDefects in insulin secretion and insulin resistance
Seen in all populationsUsually in populations with high prevalence of T2DM
Responds better to sulfonylureasResponds better to metformin
Differences between MODY and Early Onset Type 2 Diabetes (Table)

Maturity onset diabetes of the young (MODY)

  • Monogenic form of diabetes with mutation in a single gene
  • Genetic analysis is needed to confirm the diagnosis  
  • This particular patient and all members of the maternal side of her family who had diabetes were found to carry a novel mutation in MODY3(HNF 1alfa gene)
  • Genetic screening is needed to confirm the diagnosis of MODY but is nor widely available at present.
  • Mutation in Single gene.
  • Patients usually non-obese (age <25)
  • AD inheritance involving 3 generations & No Ketosis
  • Do not need insulin initially – later may become insulin-requiring [MODY 1(HNF4a), MODY3 (HNF1a)]
  • Isolated mild fasting hyperglycemia-MODY2-no treatment required
  • Diabetes with renal cysts/renal agenesis RCAD (renal cysts and diabetes syndrome)-MODY 5

What was done in this case:

Insulin Dilemma in Young Diabetics
Insulin Dilemma in Young Diabetics

GCK patients do not need treatment GCK patients untreated for 50 yrs. have no significant microvascular complications.

Insulin Dilemma in Young Diabetics

Glucokinase – all patient has similar mildly raised fasting blood glucose values.

Insulin Dilemma in Young Diabetics

Case 4

  • A young 20-year boy detected to have DM for six months back.
  • He had H/o Recurrent abdominal pain and passing oily stools for 1-2 years. Asso with 10 kg weight loss in 1yr
  • No Past H/o DKA/DK
  • No F/H of DM, Nonalcoholic, non-smoker
  • Was on OHAs (Triple Drug combination) but was uncontrolled.
  • FBG: 208, PPBG: 345mg%, HbA1c: 12.8%
  • Which next investigation should we do?
  • Height: 168cm, Weight: 50.8 kg, BMI: 18 kg/m2
  • Lipids: Normal,
  • KFT, LFT, TSH, Hemogram, Ketonuria: Absent
  • CXR Normal, ECG: WNL
  • USG Abdomen: Fatty Liver
  • Fasting C-Peptide: 0.7 pmol/ml


IMPRESSION: POOR BETA CELL FUNCTION

What is your next step towards diagnosis?

Insulin Dilemma in Young Diabetics

Clinical diagnosis: FCPD Uncommon form of “pancreatic” diabetes found in certain parts of India Most commonly found in Kerala and Tamil Nadu states; etiology unknown

Management

Insulin: Basal Bolus Therapy/Pancreatic Enzyme supplements

Diagnostic Criteria

  • Patient usually from a tropical country
  • Evidence of chronic pancreatitis should be present
  • Pancreatic Calculi on plain x-ray abdomen
  • Recurrent abdominal pain since childhood
  • Lean patient (BMI<18kg/m2)
  • History of oily stools and recurrent pain in abdomen
  • Absence of ketosis in spite of high blood sugars
  • Severe diabetes (FPG>200mg)
  • Steatorrhea
  • Abnormal pancreatic function tests
  • Absence of other causes of chronic pancreatitis viz. alcoholism, hepatobiliary disease etc.
  • Significantly increased risk of pancreatic carcinoma

Case 5

  • 32-year-old Man Presented with
  • Polyuria, Polydipsia, Polyphagia
  • FPG 202
  • PPPG 320
  • HbA1c 9.9%
  • On Examination Acanthosis was present.
  • GAD Antibody Positive
  • ICA (Islet Cell Antibody) Positive

Do you think is it Latent Autoimmune Diabetes of Adults?

Insulin Dilemma in Young Diabetics

Diabetes with the phenotypic characteristics of Type 2 Diabetes but with the immune markers, usually autoantibodies, characteristic of Type 1 Diabetes.

Insulin Dilemma in Young Diabetics

LADA is a hybrid of T1D and T2D genetically and phenotypically Initially patients of LADA, are controlled on Metformin & or sulphonyl ureas, but gradually they require Insulin, as Beta cell reserve is LOW in these patients.

Final Inputs:

Insulin Dilemma in Young Diabetics
Acanthosis Nigricans

Flow Chart to Proceed

Insulin Dilemma in Young Diabetics
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