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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 5  |  Issue : 2  |  Page : 90-94

Prolonged type 1 diabetes honeymoon period: Case report and review of the literature


College of Medicine, King Saud Bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center; Department of Medicine, Division of Endocrinology, Ministry of National Guard, Health Affairs, Riyadh, Saudi Arabia

Date of Submission27-Oct-2020
Date of Decision18-Nov-2020
Date of Acceptance29-Nov-2020
Date of Web Publication25-Feb-2021

Correspondence Address:
Dr. Moeber Mohammed Mahzari
Department of Medicine, Division of Endocrinology, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Mail Code 3130, P.O. Box 3660, Riyadh 11481
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/KKUJHS.KKUJHS_23_20

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  Abstract 

The clinical and biochemical variables of a patient with unusual and relatively long? type 1 diabetes (T1DM) remission are reported. The case is followed by literature review of interventions with a positive impact on T1DM remission. The patient has clinical and biochemical phenotype consistent with T1DM. He refused to take treatment for diabetes. He has been using Trigonella foenum-graecum as the only treatment for diabetes. The patient has not developed diabetic ketoacidosis until the time of this report (34 months after his initial diagnosis), which is unusual for patients with T1DM. The positive effect of Trigonella foenum-graecum on T1DM remission in this patient is not ascertained but possible. Relevant literature of studies and case reports of similar prolonged T1DM remission reviewed and summarized. There is a clear need to continue exploring interventions in prospective studies to induce and prolong T1DM remission.

Keywords: Honeymoon period, Trigonella foenum-graecum, type 1 diabetes


How to cite this article:
Mahzari MM. Prolonged type 1 diabetes honeymoon period: Case report and review of the literature. King Khalid Univ J Health Sci 2020;5:90-4

How to cite this URL:
Mahzari MM. Prolonged type 1 diabetes honeymoon period: Case report and review of the literature. King Khalid Univ J Health Sci [serial online] 2020 [cited 2021 Apr 10];5:90-4. Available from: https://www.kkujhs.org/text.asp?2020/5/2/90/309606


  Introduction Top


Type 1 diabetes (T1DM) is a consequence of autoimmune destruction of pancreatic beta cells, which leads to insulin deficiency. Insulin deficiency leading to hyperglycemia in the diabetes range occurs when around 90% or more of beta cells are destroyed.[1]

The immune destruction process involves complex interaction between T-lymphocytes, B-lymphocytes and multiple inflammatory mediators.[2] The time from the start of immune destruction of beta cells until the development of hyperglycemia and formal diagnosis of T1DM is quiet variable. Moreover, Transient remission (honeymoon period) of type 1 diabetes after diagnosis is a well-known phenomenon. During the honeymoon period, the immune destruction process of beta cells comes to a halt with transient regeneration of beta cells and normalization of insulin secretion. The exact mechanism for this phenomenon is largely unknown. Having said that, upregulation of interleukin 10 (which has an anti-inflammatory effect) has been suggested to have a role.[3] This honeymoon/remission period of T1DM could vary in length to a large extent and also could vary in significance from being complete to partial normalization of insulin secretion.[4]

Complete remission is the complete normalization of endogenous insulin secretion leading to normal glucose levels without any hyperglycemia treatment. On the other hand, partial remission could be defined as an insulin requirement of <0.5 units/kg of body weight per day and HbA1c <7%–8%. This period of remission (complete or partial) is of research interest as the mechanism underpinning this period may translate to an effective intervention to halt T1DM progression.[3],[4]

Few cases have been reported with long honeymoon period. This case report involves a patient with T1DM and a relatively long honeymoon period. The clinical and biochemical variables of the patient and review of the literature are reported.


  Case Report Top


A 16-year-old male patient presented to the primary care facility feeling unwell and with new-onset dizziness. He also described weight loss. Random glucose was 12 mmol/l, and hemoglobin A1C was 12.8%. He was referred to diabetes clinic and prescribed Glargine and Aspart insulin, but the patient did not use insulin and he did not attend diabetes clinic. Six months after his diagnosis, his laboratory investigations continue to be consistent with diabetes diagnosis. He eventually was seen in the diabetes clinic a year after his diagnosis. He reported feeling well and he denied any polyuria or polydipsia or history of diabetic ketoacidosis (DKA). He confirmed that he has no family history of either Type 1 or Type 2 diabetes. He takes no medication. However, he reported that he has been using Trigonella foenum-graecum grains daily for the last year. He grinds the seeds (7 seeds per day) then he drinks the powder with water. On examination, his body mass index is 25 kg/m2, no acanthosis Nigerians and the rest of his physical exam was normal. Laboratory work overtime is shown in [Table 1]. Of note, anti-Glutamic acid decarboxylase (GAD) antibodies were positive at diagnosis and continued to be positive during follow-ups. Moreover, genetic testing for Monogenic Diabetes of Young was done, including testing ABCC8, BLK, CEL, HNF1A, HNF4A, INS, KCNJ11, K1F11, NEUROD1, NKX2-2, PAX4, PDX1, RFX6, and ZFP57 genes and it was negative.
Table 1: Laboratory results of the patient over time

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His hemoglobin A1C a year after his initial presentation was 6.1% with no insulin. He was counseled on his diagnosis and it was explained and recommended to him to start on insulin, but he refused. During follow-ups, it was confirmed that his glucose started to go up based on self-monitoring of blood glucose and laboratory readings of serum glucose and HgA1C. However, he refused to start on insulin or even oral hypoglycemic agents. He continued to use Trigonella foenum-graecum seeds once daily as described above. Up to this point (34 months after his initial diagnosis with diabetes), he did not have DKA.


  Discussion Top


T1DM is a major burden for patients and health-care systems. Research is ongoing to modulate the immune system to prevent or induce sustainable remission of T1DM. Detailed understanding of the immune process of beta cells destruction and particularly immunologic changes that lead to the honeymoon period is an important aspect of the research task force against the disease.

This patient has phenotypic features and biochemical tests consistent with T1DM. The facts that he had no clinical signs of insulin resistance in addition to the positive anti-GAD antibodies and consistently normal to low normal insulin and C-peptide levels are consistent with a state of T1DM. The patient had a relatively long complete then partial remission of T1DM. This is despite the continued positivity of anti-GAD antibodies. He has one of the longest periods of T1DM remission that has been reported with no particular medical intervention.

The use of Trigonella foenum-graecum in diabetic patients is not uncommon in the Middle East countries. Especially in patients with type 2 DM. Trigonella foenum-graecum has been found to have anti-hyperglycemic effect.[5] Trigonella foenum-graecum also has been found to have an anti-inflammatory and immunomodulatory effect in animal studies.[6] However, its use to induce remission of type 1 DM has not been reported. Moreover, Trigonella foenum-graecum effect on humans' immune system has not been studied.

The effect of daily use of Trigonella foenum-graecum in this patient is not ascertained; however, at least he has not developed DKA without any intervention except the use of the seeds. Having said that, interventions to delay T1DM progression by inducing prolonged remission after diagnosis has been of research interest. Multiple interventions have been described in the literature. Some of the interventions resulted in no benefit like Rilonacept.[7] Other interventions, such as teplizumab and Abatacept, used to modulate the immune destruction of beta cells in newly diagnosed T1DM patients and reported success in preserving C peptide secretion.[8],[9],[10] [Table 2] includes a summary of the majority of available literature on interventions with a positive effect on prolongation of T1DM remission in its clinical definition. Of note, there is no consensus on the definition of T1DM remission (partial or complete) in the studies, which makes it difficult to compare interventions efficacy to each other. This elutes to the necessity to unify and clarify the definition of T1DM remission, at least for research purposes.
Table 2: Summary of available published articles of interventions with reported benefit on type 1diabetes remission

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Dipeptidyl peptidase-4 inhibitors and Vitamin D, for example, have been used with reported benefit in prolonging T1DM remission. The exact mechanism of these effects and the magnitude of its helpfulness is not well known.[11],[12] Other reported effective interventions are mostly immunosuppressive therapies and bone marrow transplantation [Table 2]. Prospective studies on the use of different interventions to prolong T1DM remission, especially interventions with minimal toxicities, are needed. Moreover, researches to understand the immunologic unpinning of the honeymoon period of T1DM will help to design appropriate interventions in future.


  Conclusion Top


There have been multiple interventions used to induce T1DM remission. Interventions varied from simple to major interventions with mixed outcomes. The use of Trigonella foenum-graecum in the setting of Type 2 Diabetes is well established. However, its use in the setting of T1DM is not well studied. The positive effect of Trigonella foenum-graecum on T1DM in this patient is not ascertained but possible. Prospective studies on the use of different interventions to modulate T1DM Course are of research interest, especially for interventions of limited adverse events.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Couper JJ, Haller MJ, Ziegler AG, Knip M, Ludvigsson J, Craig ME, et al. ISPAD clinical practice consensus guidelines 2014. Phases of type 1 diabetes in children and adolescents. Pediatr Diabetes 2014;15 Suppl 20:18-25.  Back to cited text no. 1
    
2.
Fitas AL, Martins C, Borrego LM, Lopes L, Jörns A, Lenzen S, et al. Immune cell and cytokine patterns in children with type 1 diabetes mellitus undergoing a remission phase: A longitudinal study. Pediatr Diabetes 2018;19:963-71.  Back to cited text no. 2
    
3.
Nagl K, Hermann JM, Plamper M, Schröder C, Dost A, Kordonouri O, et al. Factors contributing to partial remission in type 1 diabetes: Analysis based on the insulin dose-adjusted hbA1c in 3657 children and adolescents from germany and austria. Pediatr Diabetes 2017;18:428-34.  Back to cited text no. 3
    
4.
Sokolowska M, Chobot A, Jarosz-Chobot P. The honeymoon phase-what we know today about the factors that can modulate the remission period in type 1 diabetes. Pediatr Endocrinol Diabetes Metab 2016;22:66-70.  Back to cited text no. 4
    
5.
Gupta A, Gupta R, Lal B. Effect of trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: A double blind placebo controlled study. J Assoc Physicians India 2001;49:1057-61.  Back to cited text no. 5
    
6.
Gren A, Formicki G, Goc Z, Muchacka R, Knazická Z, Lukác N, Massányi P. Effects of trigonella foenum graecum on the leukocytes in diabetes mice. J Microbiol Biotechnol Food Sci 2012;2:467.  Back to cited text no. 6
    
7.
White PC, Adhikari S, Grishman EK, Sumpter KM. A phase I study of anti-inflammatory therapy with rilonacept in adolescents and adults with type 1 diabetes mellitus. Pediatr Diabetes 2018;19:788-93.  Back to cited text no. 7
    
8.
Linsley PS, Greenbaum CJ, Speake C, Long SA, Dufort MJ. B lymphocyte alterations accompany abatacept resistance in new-onset type 1 diabetes. JCI insight 2019;4.  Back to cited text no. 8
    
9.
Orban T, Bundy B, Becker DJ, Dimeglio LA, Gitelman SE, Goland R, et al., Type 1 Diabetes TrialNet Abatacept Study, Group. Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: Follow-up 1 year after cessation of treatment. Diabetes Care 2014;37:1069-75.  Back to cited text no. 9
    
10.
Perdigoto AL, Preston-Hurlburt P, Clark P, Long SA, Linsley PS, Harris KM, et al. Treatment of type 1 diabetes with teplizumab: Clinical and immunological follow-up after 7 years from diagnosis. Diabetologia 2019;62:655-64.  Back to cited text no. 10
    
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Lima-Martínez MM, Guerra-Alcalá E, Contreras M, Nastasi J, Noble JA, Polychronakos C. One year remission of type 1 diabetes mellitus in a patient treated with sitagliptin. Endocrinology, Diabetes & Metabolism Case Reports 2014;2014.  Back to cited text no. 11
    
12.
Cadario F, Savastio S, Ricotti R, Rizzo AM, Carrera D, Maiuri L, et al. Administration of vitamin D and high dose of omega 3 to sustain remission of type 1 diabetes. Eur Rev Med Pharmacol Sci 2018;22:512-5.  Back to cited text no. 12
    
13.
Pinheiro MM, Pinheiro FM, Torres MA. Four-year clinical remission of type 1 diabetes mellitus in two patients treated with sitagliptin and vitamin D3. Endocrinology, Diabetes & Metabolism Case Reports. 2016;2016.  Back to cited text no. 13
    
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Sildorf SM, Fredheim S, Svensson J, Buschard K. Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus. Case Reports 2012;2012:bcr0220125878.  Back to cited text no. 14
    
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Shen S, Li L, Ouyang J, Xu J, Zhu D. Remission induced by autologous hematopoietic stem cell transplantation in one newly diagnosed type 1 diabetes patient with diabetic ketoacidosis: A case report. J Diabetes 2012;4:359-61.  Back to cited text no. 15
    
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Davalli AM, Perego C, Folli FB, Bosi E. Long-lasting remission of type 1 diabetes following treatment with topiramate for generalized seizures. Acta Diabetol 2012;49:75-9.  Back to cited text no. 16
    
17.
Snarski E, Torosian T, Paluszewska M, Urbanowska E, Milczarczyk A, Jedynasty K, et al. Alleviation of exogenous insulin requirement in type 1 diabetes mellitus after immunoablation and transplantation of autologous hematopoietic stem cells. Pol Arch Med Wewn 2009;119:422-6.  Back to cited text no. 17
    
18.
Koivisto VA, Leirisalo-Repo M, Ebeling P, Tuominen JA, Knip M, Turunen U, et al. Seven years of remission in a type I diabetic patient: Influence of cyclosporin and regular exercise. Diabetes Care 1993;16:990-5.  Back to cited text no. 18
    
19.
Yilmaz MT, Devrim AS, Biyal F, Satman I, Arioglu E, Dinççag N, et al. Immunoprotection in spontaneous remission of type 1 diabetes: Long-term follow-up results. Diabetes Res Clin Pract 1993;19:151-62.  Back to cited text no. 19
    
20.
Malmegrim KC, de Azevedo JT, Arruda LC, Abreu JR, Couri CE, de Oliveira GL, et al. Pmc5411061 Pmc5319960; immunological balance is associated with clinical outcome after autologous hematopoietic stem cell transplantation in type 1 diabetes. PLoS One 2017;8:167.  Back to cited text no. 20
    
21.
Marek-Trzonkowska N, Mysliwiec M, Dobyszuk A, Grabowska M, Derkowska I, Juscinska J, et al. Therapy of type 1 diabetes with CD4(+) CD25(high) CD127-regulatory T cells prolongs survival of pancreatic islets Results of one year follow-up. Clin Immunol 2014;153:23-30.  Back to cited text no. 21
    
22.
D'Addio F, Valderrama Vasquez A, Ben Nasr M, Franek E, Zhu D, Li L, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in new-onset type 1 diabetes: A multicenter analysis. Diabetes 2014;63:3041-6.  Back to cited text no. 22
    
23.
Gu W, Hu J, Wang W, Li L, Tang W, Sun S, et al. Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes. Diabetes Care 2012;35:1413-9.  Back to cited text no. 23
    



 
 
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