Fig. 1Pathogenetic features and their relation to define diabetes. T1DM, type 1 diabetes mellitus; LADA, latent autoimmune diabetes in adults; T2DM, type 2 diabetes mellitus [32].
Fig. 2Potential pathological pathways of latent autoimmune diabetes in adults (LADA). Modified from Buzzetti et al., with permission from Springer Nature [13]. TCF7L2, transcription factor 7 like 2; HLA, human leukocyte antigen; INS VNTR, insulin variable number tandem repeat; PTPN22, protein tyrosine phosphatase nonreceptor 22; GADA, glutamic acid decarboxylase autoantibody; IA-2A, protein tyrosine phosphatase IA-2.
Fig. 3Algorithm for diagnosis and therapy of latent autoimmune diabetes in adults (LADA). BMI, body mass index; T2DM, type 2 diabetes mellitus; GADA, glutamic acid decarboxylase autoantibody; DPP-4, dipeptidyl peptidase 4.
Table 1Epidemiology of LADA [13]
Study |
Country |
Type of study |
No. of sample size |
Age range, yr |
Autoantibody |
Frequency of autoantibody positivity, % |
UKPDS 25 |
United Kingdom |
Clinical based |
3,672 |
25–65 |
GAD and/or ICA |
12 |
BOTNIA |
Finland |
Registry based |
1,122 |
28–83 |
GAD and/or IA-2 |
9.3 |
Ehime study |
Japan |
Clinical based |
4,980 |
>20 |
GAD |
3.8 |
ADOPT |
USA, Europe |
Clinical based |
4,357 |
30–75 |
GAD and/or IA-2 |
4.2 |
NIRAD |
Italy |
Clinical based |
5,330 |
30–75 |
GAD and/or IA-2 |
4.5 |
HUNT |
Norway |
Population based |
1,134 |
≥20 |
GAD |
10 |
Tianjin |
China |
Population based |
8,109 |
≥15 |
GAD |
9.2 |
Maioli et al. (2010) [14] |
Italy (Sardinia) |
Clinical based |
5,568 |
35–70 |
GAD |
4.9 |
Action LADA |
Europe |
Clinical based |
6,810 |
30–70 |
GAD and/or IA-2, ZnT8 |
9.7 |
LADA China |
China |
Clinical based |
5,324 |
≥20 |
GAD |
5.9 |
Maddaloni et al. (2015) [5] |
United Arab Emirates |
Clinical based |
17,072 |
30–70 |
GAD and/or IA-2 |
2.6 |
Lee et al. (2009) [16] |
Korea |
Clinical based |
1,370 |
47–62 |
GAD and/or IA-2 |
5.1 |
Park et al. (2011) [17] |
Korea |
Population based |
884 |
44–60 |
GAD and/or IA-2, ZnT8 |
4.4 |
Roh et al. (2013) [15] |
Korea |
Clinical based |
323 |
29–63 |
GAD |
5.3 |
Table 2Differences in Clinical and Genetic Features between LADA and T2DM
|
LADA |
T2DM |
Age at diagnosis |
>30 Years |
Adulthood (rarely before) |
Family history of diabetes |
Negative or positive |
Frequently positive |
HLA susceptibility |
Increased |
Mild increased |
Onset |
Subclinical (rarely acute) |
Silent/subclinical |
Rate of long-term complications at diagnosis |
Low |
High |
Risk of acute complications at diagnosis |
Low |
Mild increased |
C-peptide levels at diagnosis |
Decreased but still detectable |
Normal to increased |
Autoimmunity |
Mild increased |
Absent |
Ketosis |
Rare |
Rare |
Insulin resistance |
Increased/no change |
Increased |
β-Cell function |
Decreased |
Increased or normal |
Insulin requirement |
>6 Months after diagnosis |
Absent or years after diagnosis |
Body mass index |
Normal (rarely overweight or obese) |
Overweight or obese |
Cardiovascular risk |
Increased |
Increased |
Lipid profile |
Normal to hypertriglyceridemia |
Frequently hypertriglyceridemia and/or hypercholesterolemia |
Table 3Differences in Clinical and Genetic Features between LADA and T1DM
|
LADA |
T1DM |
Age at diagnosis |
>30 Years |
Childhood/adolescence (rarely in adulthood) |
Family history of diabetes |
Negative or positive |
Negative or positive |
HLA susceptibility |
Increased |
Importantly increased |
Onset |
Subclinical (rarely acute) |
Acute |
Rate of long-term complications at diagnosis |
Low |
Low |
Risk of acute complications at diagnosis |
Low |
Increased |
C-peptide levels at diagnosis |
Decreased but still detectable |
Non detectable (rarely decreased) |
Autoimmunity |
Mild increased |
Importantly increased |
Ketosis |
Rare |
Rare |
Insulin resistance |
Mild increased |
Absent (rarely increased) |
β-Cell function |
Decreased (−) |
Loss of function |
Insulin requirement |
>6 Months after diagnosis |
At diagnosis |
Body mass index |
Normal (rarely overweight or obese) |
Normal (or underweight) |
Cardiovascular risk |
Increased |
Increased |
Lipid profile |
Normal to hypertriglyceridemia |
Normal (especially) |