Slowly Progressive Type 1 Diabetes Treated with Metformin for Five Years after Onset

Hirata, Takumi; Shimada, Akira; Morimoto, Jiro; Maruyama, Taro

doi:10.2169/internalmedicine.52.9522

Cited by 4 publications

(2 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Metformin was used to treat five of the six patients in the S group at baseline; during the study period, the dosage was increased in two patients and was added in one patient (Table S2). We previously reported that metformin may suppress the disease course of SPIDDM/LADA more effectively than pioglitazone [ 23 ], and we subsequently experienced a patient with SPIDDM/LADA whose β-cell function was maintained for 5 years with treatment of metformin alone [ 37 ]. Metformin increases the GLP-1 level [ 38 ], which regulates lymphocyte proliferation and the maintenance of peripheral regulatory T cells [ 39 ]; given that metformin was recently reported to improve gut microbiome flora in type 2 diabetes patients [ 40 ], metformin treatment for non-insulin-dependent SPIDDM might have exerted immunomodulatory effects through gut flora modification.…”

Section: Discussionmentioning

confidence: 99%

Possible Long-Term Efficacy of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, for Slowly Progressive Type 1 Diabetes (SPIDDM) in the Stage of Non-Insulin-Dependency: An Open-Label Randomized Controlled Pilot Trial (SPAN-S)

et al. 2017

Self Cite

View full text Add to dashboard Cite

IntroductionWe tested the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in preserving the β-cell function for long-term periods in patients with slowly progressive type 1 diabetes (SPIDDM) or latent autoimmune diabetes in adults (LADA).MethodsIn the present open-label, randomized, controlled trial, 14 non-insulin-requiring diabetic patients with glutamic acid decarboxylase autoantibodies (GADAb) were randomly assigned to receive either sitagliptin (S group) or pioglitazone (P group). As a historical control, the Tokyo Study, in which non-insulin-dependent patients with SPIDDM were assigned to receive treatment by either insulin or sulfonylurea (SU), was used.ResultsOn average, the ∑C-peptide values during the oral glucose tolerance test through the follow-up periods showed a nonsignificant increase in the S group (n = 6, n = 5 at 48 months) compared to the P group (n = 5, n = 2 at 48 months). In comparison to the data in the Tokyo Study, treatment by sitagliptin significantly influenced the longitudinal changes in the ∑C-peptide values with a more increased direction than insulin or SU, especially in patients with 48 months of follow-up (p = 0.014 and p = 0.007, respectively). Although the titers of GADAb were not significantly different between the S and P groups during the study, the change ratio of the GADAb titers from baseline was significantly inversely correlated with the change ratio of the ∑C-peptide values from baseline in the S group (p = 0.003); in particular, when the GADAb titers decreased from baseline, the ∑C-peptide values frequently increased.ConclusionThe present pilot trial suggests that treatment of SPIDDM/LADA by sitagliptin, a DPP-4 inhibitor, may be more effective in preserving the β-cell function than insulin treatment for at least 4 years, possibly through the immune modulatory effects of DPP-4 inhibitors.Clinical trial registrationJapanese Clinical Trials Registry UMIN000003693.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0299-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Possible Long-Term Efficacy of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, for Slowly Progressive Type 1 Diabetes (SPIDDM) in the Stage of Non-Insulin-Dependency: An Open-Label Randomized Controlled Pilot Trial (SPAN-S)

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Candidates for combination treatment for preserving beta cell function in SPIDDM include metformin,12 which changes gut microbiota profiles, and pioglitazone, although results are inconclusive 109,110…”

Section: Prevention Strategies and Clinical Options For Spiddmmentioning

confidence: 99%

<p>Slowly Progressive Type 1 Diabetes Mellitus: Current Knowledge And Future Perspectives</p>

Nishimura¹,

Matsumura²,

Kikuno³

et al. 2019

DMSO

View full text Add to dashboard Cite

Slowly progressive type 1 insulin-dependent diabetes mellitus (SPIDDM), sometimes referred to as latent autoimmune diabetes in adults (LADA), is a heterogeneous disease that is often confused with type 1 and type 2 diabetes. As a result, there were few diagnostic criteria for this disorder until 2012, when the Japan Diabetes Society established criteria that could be used in clinical practice. A primary question is whether pathologic markers for type 1 or type 2 diabetes are present in the pancreas of patients with SPIDDM, because the phenotype of SPIDDM is similar to both type 1 and type 2 diabetes. Recent studies clarified pathologic findings in the pancreas of patients with SPIDDM, which included T-cell-mediated insulitis, a marker of type 1 diabetes; pseudoatrophic islets (islets specifically devoid of beta cells), another hallmark of type 1 diabetes; and a lack of amylin (ie, islet amyloid polypeptide) deposition to the islet cells, a pathologic marker of type 2 diabetes. In terms of preventing the loss of beta-cell function in patients with SPIDDM, several studies have shown that some drugs, including dipeptidyl peptidase-4 inhibitors, are effective. There is an increased need for early diagnosis of SPIDDM to preserve beta-cell function. This review presents updated findings on the pathogenesis and immunologic findings of the affected pancreas, diagnostic markers, risk factors for progression of beta-cell dysfunction, epidemiology, clinical features, diagnostic strategies, prevention strategies, and clinical options for patients with SPIDDM.

show abstract

Slow progression of type 1 diabetes associated with pembrolizumab and lenvatinib combination therapy in a patient with probable slowly progressive type 1 diabetes mellitus and endometrial cancer

Hazekawa,

Ishii

2024

Diabetol Int

View full text Add to dashboard Cite

Slowly Progressive Type 1 Diabetes Treated with Metformin for Five Years after Onset

Cited by 4 publications

References 22 publications

Possible Long-Term Efficacy of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, for Slowly Progressive Type 1 Diabetes (SPIDDM) in the Stage of Non-Insulin-Dependency: An Open-Label Randomized Controlled Pilot Trial (SPAN-S)

Possible Long-Term Efficacy of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, for Slowly Progressive Type 1 Diabetes (SPIDDM) in the Stage of Non-Insulin-Dependency: An Open-Label Randomized Controlled Pilot Trial (SPAN-S)

<p>Slowly Progressive Type 1 Diabetes Mellitus: Current Knowledge And Future Perspectives</p>

Slow progression of type 1 diabetes associated with pembrolizumab and lenvatinib combination therapy in a patient with probable slowly progressive type 1 diabetes mellitus and endometrial cancer

Contact Info

Product

Resources

About