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Letters: Observations

High Frequency of Type 1B (Idiopathic) Diabetes in North Indian Children With Recent-Onset Diabetes

  1. Krishnamurthy Balasubramanian, MD, DM1,
  2. Preeti Dabadghao, MD, DM1,
  3. Vijayalakshmi Bhatia, MD1,
  4. Peter G. Colman, MD2,
  5. Shane A. Gellert, BS2,
  6. Udalak Bharadwaj, PHD3,
  7. Suraksha Agrawal, PHD3,
  8. Nalini Shah, MD, DM4 and
  9. Eesh Bhatia, MD1
  1. 1Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
  2. 2Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Victoria, Australia
  3. 3Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
  4. 4Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, India
  1. Address correspondence to Eesh Bhatia, MD, Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India. E-mail: ebhatia{at}sgpgi.ac.in
Diabetes Care 2003 Sep; 26(9): 2697-2697. https://doi.org/10.2337/diacare.26.9.2697
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Islet antibody–negative or type 1B (idiopathic) diabetes constitutes 5–10% of Caucasian diabetic subjects with recent-onset type 1 diabetes (1). A study from Italy (2) failed to show clinical differences between these patients and those with antibodies. In contrast, a fulminant form of type 1B diabetes with associated exocrine pancreatic involvement, possibly secondary to viral infection, has been described in Japanese (3). There is little information on type 1B diabetes in other racial groups. Therefore, we studied the frequency and characteristics of type 1B diabetes in children of north Indian origin.

We studied all 55 children (32 male and 23 female) with recent-onset type 1 diabetes who presented at our diabetes clinic over a 10-year period. Subjects had an age at onset <20 years (9.7 ± 5.0 years [mean ± SD]), duration of diabetes <3 months (33 ± 20 days), severe hyperglycemia (plasma glucose 20.7 ± 8.6 mmol/l), and required insulin continuously after diagnosis. Chronic pancreatitis was ruled out by abdominal ultrasonography. GAD and insulinoma-associated protein 2 (IA-2) antibodies (GADAs and IA-2As) were determined by immunoprecipitation of recombinant 35S-labeled human antigen, as described previously (4). The antibody assays were included in all workshops and Immunology of Diabetes Society serum exchanges, and they have proven sensitivity and specificity. HLA typing for 12 DR antigens was performed using sequence-specific oligonucleotide probes.

GADAs were present in 23 subjects (42%), and IA-2As were only found in 18 subjects (33%). Both antibodies were absent in 25 children (45%). When compared with control subjects, the only HLA genotype associated with type 1 diabetes was DRB1*03/03 (8/41 [19.5%] vs. 1/105 [1%], odds ratio [OR] 26.4, Pc < 0.001). When children with GADAs or IA2As (type 1A diabetes) were compared with those in whom neither was present (type 1B diabetes), there were no differences in their clinical features (age at onset, duration of symptoms before diagnosis, frequency of ketosis, or BMI) or metabolic profile (plasma glucose, HbA1c, or fasting plasma C-peptide). The frequency of the HLA-DRB1* 03/03 genotype, when compared with control subjects, was increased in the type 1A (7/24 [29%] vs. 1/105 [1%], OR 44.8, P < 0.001) but not in the type 1B (1/17 [6%]) diabetic subgroup. No patient with fulminant type 1B diabetes (duration of symptoms <1 week and elevated serum trypsin) was detected. In fact, patients with type 1B diabetes had lower serum trypsin levels compared with the levels in those with type 1A diabetes (19.4 ± 11.9 vs. 29.1 ± 16.6 μg/l, P = 0.03; normal range 10–57 μg/l).

We found a far higher frequency of type 1B diabetes (45%) among children and adolescents with recent-onset type 1 diabetes than previously reported in other Caucasian populations (1). This may be related in part to the low frequency of IA-2A in the current study. This finding has also been reported earlier (4,5) and may be due to the low prevalence of HLA-DR4 in type 1 diabetic subjects in this racial group (5). Alternatively, an increase in diabetes from “nonautoimmune” causes such as viral infections, toxins, mutations in transcription factors, or subclinical pancreatitis is possible. The association of the high-risk genotype DRB1*03/03 with only type 1A diabetes suggests that different pathogenetic mechanisms may exist for type 1A and 1B diabetes in this study population. In view of the absence of the type of fulminant type 1B diabetes found in Japanese subjects in both the current study and earlier reports in other Caucasian groups (2), it is likely that type 1B diabetes will be heterogeneous in its etiology.

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References

  1. ↵
    Leslie RDG, Atkinson MA, Notkins AL: Autoantigens IA-2 and GAD in type 1 (insulin-dependent) diabetes. Diabetologia 42:3–14, 1999
    OpenUrlCrossRefPubMedWeb of Science
  2. ↵
    Pozzilli P, Visalli N, Leslie D, IMDIAB group: No evidence of rapid onset (Japanese) type 1 diabetes in Caucasian patients (Letter). Diabetologia 43:1322, 2000
    OpenUrl
  3. ↵
    Imagawa A, Hanafusa T, Miyagawa J, Matsuzawa Y: A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. N Engl J Med 342:301–307, 2000
    OpenUrlCrossRefPubMedWeb of Science
  4. ↵
    Singh AK, Bhatia E, Dabadghao P, Bhatia V, Gellert SA, Colman P: Role of islet autoimmunity in the aetiology of different clinical subtypes of diabetes mellitus in young north Indians. Diabetes Med 17:275–280, 2000
    OpenUrlPubMed
  5. ↵
    Kelly MA, Alvi NS, Croft NJ, Mijovic CH, Bottazzo GF, Barnett AH: Genetic and immunological characteristics of type 1 diabetes mellitus in an Indo-Aryan population. Diabetologia 43:450–456, 2000
    OpenUrlCrossRefPubMed
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Diabetes Care: 26 (9)

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High Frequency of Type 1B (Idiopathic) Diabetes in North Indian Children With Recent-Onset Diabetes
Krishnamurthy Balasubramanian, Preeti Dabadghao, Vijayalakshmi Bhatia, Peter G. Colman, Shane A. Gellert, Udalak Bharadwaj, Suraksha Agrawal, Nalini Shah, Eesh Bhatia
Diabetes Care Sep 2003, 26 (9) 2697; DOI: 10.2337/diacare.26.9.2697

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High Frequency of Type 1B (Idiopathic) Diabetes in North Indian Children With Recent-Onset Diabetes
Krishnamurthy Balasubramanian, Preeti Dabadghao, Vijayalakshmi Bhatia, Peter G. Colman, Shane A. Gellert, Udalak Bharadwaj, Suraksha Agrawal, Nalini Shah, Eesh Bhatia
Diabetes Care Sep 2003, 26 (9) 2697; DOI: 10.2337/diacare.26.9.2697
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