Treatment of latent autoimmune diabetes mellitus

It has been established that sulfonylurea drugs, unlike insulin, do not provide sufficient metabolic control in latent autoimmune diabetes.

Latent autoimmune diabetes of adults – slowly progressive diabetes 1   type The purpose of the analysis, the results of which were published by British authors in the journal “Cochrane database of systematic reviews”, was to compare treatment options for latent autoimmune diabetes.

Studies for analysis were selected in electronic databases, conference materials, and also through consultation with experts. Last search was conducted in December 2010 We searched for randomized controlled trials and controlled clinical trials evaluating the results of the treatment of latent autoimmune diabetes in adults or diabetes mellitus 2 type with autoantibodies. Two authors, independently of each other, were engaged in data collection and risk assessment of systematic error. Research data were combined through meta-analysis or descriptive analysis.

During the search was selected 13   306 references. The review included 15 publications (10 studies), which included 1019 participants, who were monitored for 3 years. All studies had a high risk of systematic error. Sulfonylurea drugs with insulin slightly improved metabolic control compared with insulin monotherapy for 3   months yatsy (Study 1, n = 15) and 12 months (1 study, n =14) of treatment and observation. Sulfonylurea drugs (with or without metformin) provided worse metabolic control than insulin monotherapy.

The difference between the mean values ​​of glycated hemoglobin A1c at the beginning and end of the study for insulin and oral therapy was -1.3% (95% confidence interval [CI] from -2.4 to -0.1; p = 0.03; 160 participants, 4 studies The duration of treatment / observation was 12, 30, 36 and 60 month; however, significant heterogeneity was noted). It was also found that the use of sulfonylurea drugs leads to the early formation of insulin dependence. Percentage of patients needing insulin after 2 years of treatment in the sulfonylurea group was 30%, compared with 5% in the standard treatment group (p <0.001). The share of insulin-dependent patients was 64% in the sulfonylurea group and 12.5% ​​in the insulin group ( p = 0.007).

The authors did not reveal the effect of insulin and sulfonylureas on the C-peptide level of toxins, however, insulin better supported the stimulated level of C-peptide (1 study, the difference between the mean values ​​of 7.7 ng / ml; 95% CI 2.9-12.5). When monitoring the use of GAD65 (glutamic acid decarboxylase with aluminum hydroxide) (not registered in Russia) at a dose of 20 mcg/day for 5 For years, the improvement in the levels of the lean and stimulated C-peptide levels has been maintained. In a study with an observation period of 3 month (n = 74), in which Chinese medicines were used, there were no significant differences in the improvement of C-peptide levels of Toxic compared with insulin monotherapy (0.07 µg / l; 95% CI from -0.05 to 0.19).

In a study using vitamin   D and insulin was shown to demonstrate the stability of the C-peptide toxin level in the vitamin group   D when falling from 368 to 179 pmol / l ( p = 0.006) in the insulin monotherapy group after 12  month of observation. It was difficult to compare these works because of the high level of heterogeneity of the studies and their selection criteria. No information was obtained from the selected works on health-related quality of life, complications of diabetes mellitus, treatment costs and mortality, as well as insufficient data on side effects, in particular, no cases of severe hypoglycemia were reported.

In 2 studies it was shown that sulfonylurea drugs lead to the early formation of insulin dependence. In a meta-analysis of 4 studies with significant heterogeneity, poor metabolic control was established when prescribing this group of drugs to patients with latent autoimmune diabetes. In one study, the protective effect of vitamin C was found. In combination with insulin on β-cells of the pancreas with latent autoimmune diabetes in adults. Newer drugs, such as GAD65, help to maintain a lean and stimulated C-peptide level. However, no significant data was obtained on the effectiveness of other types of diabetes treatment.

Therapy with GAD65 antigen in newly diagnosed diabetes mellitus

Swedish doctors conducted a study that did not reveal the benefits of GAD-alum over placebo in patients with type 1 diabetes.

Isoform of glutamic acid decarboxylase with a molecular weight of 65 KDa (GAD65;) is an autoantigen that plays a major role in the pathogenesis of diabetes mellitus 1 type Swedish researchers have suggested that patients with recent diabetes 1   such as GAD65 in combination with aluminum sulfate (GAD-alum; not registered in Russia) can contribute to the preservation of the functional activity of β-cells of the pancreas.

The authors investigated 334 patients aged 10-20 years with diabetes 1 type, in which there was a decrease in the concentration of C-peptide below 0.3   ng / ml (0.1   nmol / l), and in serum autoantibodies to GAD65 were determined. Within 3   Months after the diagnosis was made, patients were randomized to treatment using one of three regimens: 4 doses of GAD-alum, 2 doses of GAD-alum + 2 doses of placebo, or 4 doses of placebo. The primary endpoint was a change in the stimulated level of serum C-peptide (after the glucose tolerance test with mixed food) for 15 months since the initial visit.Secondary points were glycated hemoglobin level, average daily insulin dose, hypoglycemia rate, and C-peptide level measured on an empty stomach and after maximum stimulation. The research results are published in the New England Journal of Medicine.

Stimulated C-peptide levels decreased to the same extent in all groups that participated in the study. Primary outcome after 15   The month also did not differ much between the groups receiving the combination therapy with the active drug and only placebo ( p = 0.10). The use of GAD-alum, compared with placebo, did not affect the insulin dose, the level of glycated hemoglobin and the frequency ofhypoglycemia. Side effects were rare and occurred in mild form in all three groups.

GAD-alum does not contribute to a significant decrease in stimulated C-peptide and after 15 Month of administration does not improve the outcome of the disease.

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