Interventions for latent autoimmune diabetes (LADA) in adults

Abstract

Latent autoimmune diabetes in adults (LADA) is a slowly developing type 1 diabetes. To compare interventions used for LADA. Studies were obtained from searches of electronic databases, supplemented by handsearches, conference proceedings and consultation with experts. Date of last search was December 2010. Randomised controlled trials (RCT) and controlled clinical trials (CCT) evaluating interventions for LADA or type 2 diabetes with antibodies were included. Two authors independently extracted data and assessed risk of bias. Studies were summarised using meta‐analysis or descriptive methods. Searches identified 13,306 citations. Fifteen publications (ten studies) were included, involving 1019 participants who were followed between three months to 10 years (1060 randomised). All studies had a high risk of bias. Sulphonylurea (SU) with insulin did not improve metabolic control significantly more than insulin alone at three months (one study, n = 15) and at 12 months (one study, n = 14) of treatment and follow‐up. SU (with or without metformin) gave poorer metabolic control compared to insulin alone (mean difference in glycosylated haemoglobin A1c (HbA1c) from baseline to end of study, for insulin compared to oral therapy: ‐1.3% (95% confidence interval (CI) ‐2.4 to ‐0.1; P = 0.03, 160 participants, four studies, follow‐up/duration of therapy: 12, 30, 36 and 60 months; however, heterogeneity was considerable). In addition, there was evidence that SU caused earlier insulin dependence (proportion requiring insulin at two years was 30% in the SU group compared to 5% in conventional care group (P < 0.001); patients classified as insulin dependent was 64% (SU group) and 12.5% (insulin group, P = 0.007). No intervention influenced fasting C‐peptide, but insulin maintained stimulated C‐peptide better than SU (one study, mean difference 7.7 ng/ml (95% CI 2.9 to 12.5)). In a five year follow‐up of GAD65 (glutamic acid decarboxylase formulated with aluminium hydroxide), improvements in fasting and stimulated C‐peptide levels (20 μg group) were maintained after five years. Short term (three months) follow‐up in one study (n = 74) using Chinese remedies did not demonstrate a significant difference in improving fasting C‐peptide levels compared to insulin alone (0.07 µg/L (95% CI ‐0.05 to 0.19). One study using vitamin D with insulin showed steady fasting C‐peptide levels in the vitamin D group but declining fasting C‐peptide levels (368 to 179 pmol/L, P = 0.006) in the insulin alone group at 12 months follow‐up. Comparing studies was difficult as there was a great deal of heterogeneity in the studies and in their selection criteria. There was no information regarding health‐related quality of life, complications of diabetes, cost or health service utilisation, mortality and limited evidence on adverse events (studies on oral agents or insulin reported no adverse events in terms of severe hypoglycaemic episodes). Two studies show SU leading to earlier insulin dependence and a meta‐analysis of four studies with considerable heterogeneity showed poorer metabolic control if SU is prescribed for patients with LADA compared to insulin. One study showed that vitamin D with insulin may protect pancreatic beta cells in LADA. Novel treatments such as GAD65 in certain doses (20 μg) have been suggested to maintain fasting and stimulated C‐peptide levels. However, there is no significant evidence for or against other lines of treatment of LADA. LADA（成人隐匿性自身免疫性糖尿病）的干预措施 LADA （成人隐匿性自身免疫性糖尿病）是一种进展缓慢的1型糖尿病。 比较不同干预措施对LADA的效果。 检索电子数据库，辅以手工检索、会议论文检索和专家咨询。检索时间截至2010年12月。 纳入评价不同干预措施对LADA或2型糖尿病伴胰岛素抗体的疗效的随机对照试验和临床对照试验。 由两名评价者独立提取数据并进行偏倚风险评价。采用Meta‐分析或描述性研究方法总结结果。 初检结果13,306条，最终纳入10项研究发表的15篇文献（n=1019，其中1060例为随机分配），随访时间从3个月至10年不等。所有研究均存在较高的偏倚风险。分别治疗和随访3个月（1项研究，n=15）或12个月（1项研究，n=14）的试验中，与单独使用胰岛素相比，SU（磺脲）与胰岛素联用并未显示更明显的代谢控制效果。与单用胰岛素相比，SU（单用或与metformin（二甲双胍）联用）的代谢控制效果较差（使用HbA1c（糖化血红蛋白A1c）均数差（MD）进行统计描述，4个研究（n=160）发现胰岛素治疗与口服降糖药相比，MD=−1.3% (95% CI: −2.4 ∼ −0.1; P = 0.03，治疗或随访时间分别为12个月、30个月、36个月及60个月；但各研究间存在明显的异质性)。此外，有证据表明，使用SU可导致更早发生胰岛素依赖（SU治疗组第二年需胰岛素治疗的患者达30%，而常规治疗组为5%（P<0.001）；SU组被确定为胰岛素依赖的患者高达64%，而胰岛素治疗组为12.5%（P=0.007））。虽然未发现这些干预措施能影响空腹C肽水平，但与SU相比，胰岛素维持餐后C肽水平的效果更好（一项研究，MD=7.7 ng/ml （95% CI: 2.9 ∼ 12.5））。 在对GAD65（谷氨酸脱羧酶‐氢氧化铝合剂）治疗组随访5年后，发现其对空腹C肽和餐后C肽水平（20 μg组）的改善效果稳定。一项短期（3个月）随访研究（n=74）显示，与单独使用胰岛素相比，中医药疗法对改善空腹C肽水平无显著差异（0.07 μg/L ，95% CI: −0.05 ∼ 0.19)。而另一项随访12个月的研究结果显示，维生素D与胰岛素联用可维持稳定的空腹C肽水平，而单独使用胰岛素则空腹C肽水平有所下降（从368pmol/L降至179 pmol/L，P =...