Six-year follow-up of pancreatic beta cell function in adults with latent autoimmune diabetes

Abstract

Aim: To investigate the characteristics of the progression of islet beta cell function in Chinese latent autoimmune diabetes in adult (LADA) patients with glutamic acid decarboxylase antibody (GAD-Ab) positivity, and to explore the prognostic factors for beta cell function.

Methods: Forty-five LADA patients with GAD-Ab positivity screened from phenotypic type 2 diabetic (T2DM) patients and 45 T2DM patients without GAD-Ab matched as controls were followed-up every 6 mo. Sixteen patients in LADA1 and T2DM1 groups respectively have been followed-up for 6 years, while 29 patients in LADA2 and T2DM2 groups respectively for only 1.5 years. GAD-Ab was determined by radioligand assay, and C-peptides (CP) by radioimmune assay.

Results: The percentage of patients whose fasting CP (FCP) decreased more than 50% compared with the baseline reached to 25.0% at 1.5(th) year in LADA1 group, and FCP level decreased (395.8+/-71.5 vs 572.8+/-72.3 pmol/L, P<0.05) at 2.5(th) year and continuously went down to the end of follow-up. No significant changes of the above parameters were found in T2DM1 group. The average decreased percentages of FCP per year in LADA and T2DM patients were 15.8% (4.0-91.0%) and 5.2% (-3.5 to 35.5%, P=0.000) respectively. The index of GAD-Ab was negatively correlated with the FCP in LADA patients (r(s)=-0.483, P=0.000). The decreased percentage of FCP per year in LADA patients were correlated with GAD-Ab index, body mass index (BMI) and age at onset (r(s)=0.408, -0.301 and -0.523 respectively, P<0.05). Moreover, GAD-Ab was the only risk factor for predicting beta cell failure in LADA patients (B=1.455, EXP (B)=4.283, P=0.023).

Conclusion: The decreasing rate of islet beta cell function in LADA, being highly heterogeneous, is three times that of T2DM patients. The titer of GAD-Ab is an important predictor for the progression of islet beta cell function, and age at onset and BMI could also act as the predictors.

Figure 1

Changes of FCP level in LADA1 and T2DM1 patients during the 6-year follow-up time. Values are mean±SE of 16 patients respectively. The lower line shown here is representative of LADA patients and the upper one of T2DM group’s. The FCP of LADA1, decreasing much quicker than that of T2DM1 patients, declined significantly from the 30^th mo compared with the entry (^aP<0.05, ^bP<0.01). And from the 12^th mo, the difference of FCP between LADA1 and T2DM1 patients became significant until the end of follow-up time (^cP<0.05, ^dP<0.01). Meanwhile T2DM1 group did not show any significant decrease during the follow-up period (P>0.05).

Figure 2

The percentage of patients whose FCP decreased more than 50% compared with the baseline during the follow-up time. Black bar graph representing the percentage of LADA patients, which showed us a much quicker increase from 6.25% at 6^th mo to 25.0% at 18^th mo until 93.8% at 72^th mo. Meanwhile in the white bar of T2DM group, the percentage increased much slower and only to 30.0% at the end of follow-up.

Figure 3

The failure of islet function during the follow-up in LADA patients. The number of patients with β cell failure increased from 0/9 (new onset) to 1/18 (2-year duration), 2/15 (3-year duration), 5/24 (4-year duration), 5/20 (5-year duration), 6/12 (6-year duration) and 8/11 (7-year duration). The average time for β cell failure was 4.4±1.9 years.

Figure 4

Correlation of FCP level and GAD-Ab index in LADA patients. The X-axis represented GAD-Ab index that ranged from 0.05 to 1.91 and the Y-axis showed the FCP that ranged from 111 to 1 194 pmol/L of 45 LADA patients at enrollment. The scatter diagram showed us that these two factors were negatively correlated (r = -0.483, P = 0.001), which meant that the LADA patients with much higher GAD-Ab titer would face more risk of islet function failure.

Figure 5

Survival analysis of the cumulative failure rates of islet β cell function in LADA and T2DM patients during the follow-up period. The X-axis represented the duration of diabetes and Y-axis meant the cumulative proportion of β cell failure in these patients. Patient that developed β cell failure would be supposed as “dead”, otherwise, as “survival” at different period of duration (called “survival time”). The dotted and the solid line represented LADA and T2DM patients respectively. The β cell failure cumulative rate increased from 0.074 at the 2^nd year to 0.462 at the 8^th year of duration in LADA patients; however, that of T2DM remained unchangeable in the whole period.