alexa Cessation of Multiple Daily Insulin Injections in a Person with Twenty-Nine Years of “Type 1 Diabetes” | Open Access Journals
ISSN: 2572-5629
Diabetes Case Reports
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Cessation of Multiple Daily Insulin Injections in a Person with Twenty-Nine Years of “Type 1 Diabetes”

Joel LIM Guanyi1, Su Fen ANG1, Clara Tan SH1, and Jessie Fong CW1, Su Chi LIM1,2*

1Clinical Research Unit, Khoo Teck Puat Hospital, Singapore

2Diabetes Centre, Khoo Teck Puat Hospital, Singapore

*Corresponding Author:
Su Chi LIM
Clinical Research Unit
Khoo Teck Puat Hospital, Singapore
Tel: +65-66022353
E-mail: [email protected]

Received date: March 12, 2017; Accepted date: March 27, 2017; Published date: March 30, 2017

Citation: Su Chi LIM, Joel LIM G, Su Fen ANG, Clara Tan SH, Jessie Fong CW (2017) Cessation of Multiple Daily Insulin Injections in a Person with Twenty-Nine Years of “Type 1 Diabetes”. Diabetes Case Rep 2:122.

Copyright: © 2017 Su Chi LIM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Diabetes Case Reports

Abstract

Diabetes mellitus is a complex and etiologically heterogeneous metabolic disorder. Therefore, accurate classification of patients into diabetes-subtypes remains a challenge in clinical practice. We report a 50-year-old, non-obese (Body Mass Index (BMI) 22.4 kg/m2) Chinese lady who was diagnosed with Type 1 Diabetes Mellitus (T1DM) at age 21. This diagnosis was made owing to abnormal glucose tolerance detected during pregnancy and the young-onset nature of the disease. Subsequently, a multiple daily insulin injection (MDI) regime was initiated and maintained for almost three decades. Given a few clinical features atypical of T1DM (i.e. relatively stable fasting and post-absorptive glucose profile along with being non-ketotic prone despite occasional interruption of MDI, suggesting preserved pancreatic β cell insulin secretory function), the diagnosis was re-visited. She was subjected to deep re-sequencing of a panel of 16 candidate genes implicated in monogenic diabetes (or Maturity Onset Diabetes of the Young [MODY]) using Next Generation Sequencing (NGS) technology. A glucokinase (GCK) coding non-synonymous mutation (S441W), novel among Asians was discovered. The mutation was predicted to be functionally deleterious by multiple bioinformatics algorithms. Additionally, one recent in vitro site-directed mutagenesis study reported reduced enzyme-substrate (i.e. glucose) affinity associated with this variant. This suggested a revised diagnosis of MODY2. Notwithstanding the long-standing duration of diabetes, she was successfully weaned off from all anti-diabetic agents over the next few months with modest impact on her global glycemic profile (HbA1c 6.4% to 6.9%). Averting unnecessary long-term pharmacotherapy often means substantial health-cost savings, avoidance of potential treatment-related adverse-effects and importantly, better quality of life for the person and their family members. This case-report serves as an important reminder to reconsider the diagnosis and consider the option of genetic testing (especially in the era of NGS), among diabetic individuals with features atypical of the classic forms of diabetes.

Keywords

Maturity onset diabetes of the young (MODY); Misdiagnosis; Next-generation sequencing (NGS); Glucokinase (GCK) mutation

Introduction

Diabetes is traditionally thought to be an etiologically-complex disorder stemming from the culmination of many factors including impaired insulin action and defect in pancreatic β-cell insulin secretion. Individualized therapeutics that effectively addresses the root cause is therefore challenging, and at times elusive. There is however, a subset of patients who suffer from diabetes resulting predominantly from a single gene mutation i.e. monogenic diabetes or traditionally called-maturity onset diabetes of the young (MODY). Each mutation has a high degree of penetrance, resulting in high blood glucose concentration characteristic of diabetes. While the genetic architecture of MODY continue to evolve, well established major candidate genes include Glucokinase (GCK), hepatic nuclear factor (HNF)1α, HNF4α and HNF1β, which collectively explain more than 90% of all MODY in most population [1]. Guided by precise molecular diagnosis, treatment targeting the root cause is likely to be more effective i.e. precision medicine. Unfortunately, such patients are often misdiagnosed as suffering from the more common T1DM (or young-onset type 2 diabetes (T2DM)) due to the young age of onset of the disease. Consequently, insulin treatment is often initiated and maintained indefinitely with unintended consequences.

Case Report

A non-obese (with body mass index (BMI) 22.4 kg/m2) 50-year-old Chinese lady was diagnosed with Type 1 Diabetes Mellitus (T1DM) at age 21, owing to abnormal glucose tolerance detected during pregnancy. Subsequently, multiple daily insulin (MDI) injections of long-acting insulin Detemir 10 u bed time and short-acting insulin Lispro 2 u TDS were given. This resulted in stable glycemic control (HbA1c hovering around the range of 6.4% to 7.2%) for close to three decades.

She was referred to a secondary care diabetes center for consideration of continuous subcutaneous insulin infusion (CSII) therapy with the aim of more consistently achieving a HbA1c target of ≤6.5%. However, unlike individuals with longstanding T1DM (or T2DM), she had a very stable fasting and post-absorptive (pre-meal) glucose profile largely hovering around 5.0 mmol/L [2,3] (Table 1). Additionally, she was non-ketotic prone despite occasional interruption of MDI. These clinical features suggested preserved pancreatic β-cell insulin secretory function atypical of an individual with longstanding T1DM (or T2DM). Furthermore, she was tested negative for glutamic acid decarboxylase (GAD) antibody-a maker of T1DM associated β-cell autoimmunity, known to be fairly durable among Asians [4]. Therefore, the diagnosis of T1DM was re-visited.

Breakfast Lunch Dinner
Pre Post Pre Post Pre Post
5.1 7.7 5.2 8.0 4.9 6.9
5.0 8.1 4.8 7.4 5.1 8.3
4.9 7.9 5.6 8.2 5.5 7.5
5.2 8.2 5.4 9.9 5.3 8.4
5.1 7.8 5.5 8.8 5.2 9.3

Table 1: Self glucose monitoring results showing very stable fasting and postabsorptive (pre-meal) blood glucose (in mmol/L) profile, consistent with preserved pancreatic Ã-cell insulin secretory function, which is atypical of an individual with longstanding âType 1 Diabetesâ.

The patient was enrolled in a monogenic diabetes pilot study [5].A panel of 16 candidate genes commonly implicated in monogenic diabetes were deep re-sequenced using Ion Torrent PGMTM (Life Technologies) with an average read-depth of 100 times. These 16 candidate genes include 13 known MODY genes (GCK, HNF1A, HNF4A, HNF1B, NEUROD1, INS, CEL, PDX1, PAX4, BLK, KLF11, KCNJ11 and ABCC8), one insulin resistance gene (INSR) and two lipodystrophy associated diabetes genes (LMNA and PPARG). A GCK coding non-synonymous mutation (S441W), novel in Asian populations, was discovered and subsequently confirmed by bidirectional Sanger capillary sequencing technology. The mutation was predicted to be functionally deleterious by open-resource bioinformatics tools SIFT and PolyPhen-2. The GCK gene codes for glucokinase which phosphorylates glucose to glucose 6-phosphate. This takes place in the first step of the glycolysis pathway, metabolizing glucose to release its stored energy. By means of this reaction, glucokinase functions as the glucose sensor of pancreatic β-cells [6]. The missense mutation, substituting tryptophan for serine at position 441, decreases the glucose affinity of glucokinase [7], thereby leading to a right-shift in the β-cell glucose-sensitivity. Therefore, glucose homeostatic mechanisms are still functional albeit at a mildly elevated glucose set-point. Hence, the patient was re-diagnosed as having MODY2 and was advised to wean off insulin replacement therapy.

To ensure safety, a stepwise insulin reduction algorithm was adopted. Therefore, the prandial ultra-rapid action insulin-Lispro was first omitted for breakfast. When glucose monitoring suggested blood glucose profile to be no different from previous values after 3 days, insulin-Lispro was then omitted for lunch. Likewise, prandial insulin at dinner was omitted 3 days later. Patient’s preference was to be kept on bedtime Detemir 10 u for a few more weeks to ensure no ketosis. Subsequently, Detemir was stepwise-reduced by 2 units every week till total daily dose of 4 units, which was stopped when fasting glucose remained stable. Hence, despite almost 3 decades of MDI treatment, she was completely taken off insulin successfully (Figure 1).

diabetes-case-reports-multiple-daily-insulin-injections

Figure 1: Serial HbA1c before and after stepwise weaning and eventual cessation of multiple daily insulin injections (MDI).

Discussion

There are several clinical lessons to be gleaned from this casereport

Firstly, awareness of the etiological heterogeneity of diabetes mellitus needs greater highlight among clinicians. Notwithstanding its high prevalence, diabetes remains a challenge which defies accurate classification. In the clinics, it is not uncommon to meet patients with features atypical of the classic forms of type 1 or 2 diabetes [8]. Therefore, high degree of awareness of less common diabetes-subtype, assisted by web-based open-resources such as the “MODY-calculator” may help identify individuals eligible for genetic testing [9]. High-throughput NGS may potentially revolutionize the diagnostic algorithm of diabetes thereby ushering in the era of pharmacogenetics i.e. precision medicine for diabetes [10,11].

Secondly, the present recommendation to actively screen for gestational diabetes (GDM) with a set of strict blood glucose criteria among expecting women can be exploited to facilitate the case-finding for MODY2 [12]. Therefore, expecting women with glucose intolerance harboring clinical features atypical of GDM (e.g. slim individual, as in our case-report) may warrant consideration of other form of diabetes such as MODY2. Given the potential implication of fetal growth and glycemic management during pregnancy in the setting of maternalfetal discordance in GCK mutation status, confirming the diagnosis of MODY2 is not just an academic exercise [13]. Hence, stake-holders in the field of GDM may wish to incorporate case-finding for MODY2 in the overall diagnostic workup.

Thirdly, careful consideration should be made to modify treatment (in this case, gradual cessation of insulin) informed by the genetic diagnosis (i.e. MODY2). It has been reported that MODY2 requires no specific pharmaco-therapeutics. Importantly, the omission of antidiabetic treatment does not lead to vascular complications among these subjects despite a median duration of 48.6 years of hyperglycemia [14,15]. Therefore, the most appropriate treatment based on accurate diagnosis often means substantial health-cost savings, avoidance of potential treatment-related adverse-effects and importantly, better quality of life for the person and their family members [16].

Acknowledgement

We would like to thank the patient for her participation and members of the KTPH Diabetes Centre for their support. This study is funded by National Healthcare Group (NHG)-Khoo Teck Puat Hospital (KTPH) Small Innovative Grants: SIGI/13038 and SIGII/14001.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 259
  • [From(publication date):
    April-2017 - Aug 24, 2017]
  • Breakdown by view type
  • HTML page views : 227
  • PDF downloads :32
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords