Clinical Heterogeneity of Diabetes in Young Korean Patients

Yongsoo Park

doi:10.4093/jkd.2014.15.4.190

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Park: Clinical Heterogeneity of Diabetes in Young Korean Patients

Statement

J Korean Diabetes 2014;15(4):190-195.

Published online: 20 January 2014

DOI: https://doi.org/10.4093/jkd.2014.15.4.190

Clinical Heterogeneity of Diabetes in Young Korean Patients

Yongsoo Park

Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Diabetes among young patients in Korea is caused by a complex set of factors. In addition to the typical T1aD and T2D patients, there is a variable incidence of cases of non-autoimmune types of T1D associated with insulin deficiency (T1b), such as fulminant T1D (FT1D). Although T1a is the major type of childhood diabetes, FT1D exists as a hyper-acute subtype of T1D that affects older children, without causing autoimmunity. They showed a complete loss of β-cell secretory capacity without evidence of recovery, necessitating long-term treatment with insulin. In addition, latent autoimmune diabetes in adults (LADA) is a form of autoimmune-mediated diabetes, usually diagnosed based on GAD autoantibody positivity. Although many epidemiological surveys of LADA have been conducted in Caucasian and Asian populations, their reported prevalence rates vary due to the use of different diagnostic criteria. In a recent study with a comparable design and valid methodology, the prevalence of LADA using GAD autoantibody positivity as the diagnostic criterion was higher (4.4%) than the previously reported prevalence of 1.7% in a population-based T2D survey. After 36 months of follow-up, only 3 of the 39 patients initially diagnosed with LADA had become insulin-dependent, and they were all positive for multiple autoantibodies (GAD, IA-2 and ZnT8 antibody). This demonstrates that true insulin dependency, which was initially indicated by multiple antibody positivity, has not increased in the Korean population. Therefore, despite etiological heterogeneity, in the clinical setting, early diagnosis and classification of patients with diabetes relying on clinical grounds without measuring autoantibodies could be a possible method to minimize complications.

Keywords: Genetic heterogeneity, Diabetes mellitus type 1, Latent autoimmune diabetes in adults, Autoantibodies

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Fig. 1.

Approach to the treatment of the Asian adolescent with diabetes.

Table 1.

Varying selection criteria for LADA

Study name	Age criteria	Onset diagnosis	Autoimmune evidence	C-peptide	History of ketoacidosis	Comments
Sweden (Agardh, 2005)	30–70 yr	Type 2	GAD antibody positivity	Detectable C-peptide	Not specifically mentioned	Diagnosed within past 5 years and not requiring insulin
Cuba (Cabrera-Rode, 2002)	None given	Type 2	GAD and ICA positive	–	No ketoacidosis (in one month) treated with insulin and sulfonylureas	Divided into disease durations of up to 3 years and 3 + years
Japan (Kobayasahi, 1996)	None given	Type 2	ICA positive	–	No ketoacidosis or initial need for insulin
Japan (Maruyama, 2003)	None given	Diabetes not treated with insulin	GAD positive	–	No ketoacidosis	Not treated with insulin for at least 6 months after diagnosis. Disease duration less than 10 years
China (Zhou, 2005)	Over 25 yr	Diabetes	GAD positive	Fasting C-peptide of 0.3 mmol/L or more	No ketoacidosis within 6 months of diagnosis	Disease duration less than 5 years
Sweden (Thunander, 2010)	Over 30 yr	Type 2	GAD or ICA positive	–	Not specifically mentioned	Not insulin requiring at onset
China (Zhou, 2010)	25–70 yr	Diabetes	GAD positive	Fasting C-peptide level of 0.2 nmol/L or more	No ketoacidosis within the first 6 months after diagnosis of diabetes	Disease duration less than 3 yr. Fasting C-peptide of 0.2 mmol/L or more

LADA, latent autoimmune diabetes in adults; GAD, glutamic acid decarboxylase; ICA, islet cell antibody.

Table 2.

Comparison of different treatments for LADA

Study name	Comparison of treatments	No.	HbA1c at 0 to 12 months^a	Fasting c-peptide at 0 to 12 months^a	Comments
UK (Davis, 2005)	Insulin vs. sulfonylurea (FBG < 15 mmol/L)	235 (all patients type 2 and LADA)	0.4%	–	CI cannot be calculated
Sweden (Agardh, 2005)	Diamyd (GAD65) (20 ug or 100 ug or 500 ug) vs. Placebo/ 4 ug diamyd	47	0.08% (0.4 to 0.7)	–
Japan (Maruyama, 2008)	Insulin vs. sulfonylurea	60	–0.5 (−1.33 to 0.33)	–
China (Yang, 2009)	Insulin vs. insulin + rosiglitazone (GAD Ab > 175 U/mL and fasting c-peptide > 3 nmol/L)	24	2.01 (0.15 to 3.87)	–
China (Zhou, 2005)	Insulin vs. insulin + rosiglitazone	17	+1.2%	–0.4	Estimates based on median values
China (Li, 2009)	Insulin vs. insulin + vitamin D	35	–	100 pmol/L	CI cannot be calculated
Sweden (Thunander, 2010)	Insulin vs. diet +/- metformin and/or sulfonylurea	37	0.4 (−0.38 to 1.18)	–	Stimulated C-peptide only reported
China (Zhou, 2010)	Insulin vs. insulin + sitagliptin	30	No change	110 pmol/L

^a Difference in means between groups at study end.

LADA, latent autoimmune diabetes in adults; FBG, fasting blood glucose; CI, confidence interval; GAD, glutamic acid decarboxylase.

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