Gravicentric approach to Type 2 Diabetes therapy. The success prediction. A proof-of-concept
- Authors: levit S.1,2, Torban N.3, Boaz M.4,5, Weichman M.6, Azuri J.7,8, Manisterski Y.9,10, Merzon E.11,8, Ryder D.1, Ginossar G.12, Gavra T.13, Levit V.14, Domuschiev I.15, Musin I.2, Ryder C.H.16,17
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Affiliations:
- Endocrinology and Diabetology Institute affiliated to Assuta Medical Center, Tel Aviv, Israel
- Kazan National Research Technological University, Kazan, Russia
- Institute of Endocrinology, Diabetes & Metabolism, Assuta Medical Center, Tel Aviv, Israel
- Department of Nutrition, School of Health Sciences, Ariel University Ariel, Israel
- Epidemiology and Research Unit, E. Wolfson Medical Center, Holon, Israel
- Maccabi Health Foundation, Petah – Tiqwa, Israel
- Maccabi Healthcare Services
- Lecturer of Sackler Faculty of Medicine, Tel Aviv, Israel
- Maccabi Health Foundation
- Petah – Tiqwa, Israel
- Leumit Health Foundation, Tel Aviv, Israel
- Urgent Care Consultant the Royal London Hospital, A&E and Urgent Care Centre, London, United Kingdom
- Assuta Medical Centers, Tel Aviv University, Tel Aviv, Israel
- City Clinical Hospital No8, Chelyabinsk, Russia
- Multiprofile Hospital for active treatment “St. Panteleimont”, Sofia, Bulgaria
- Department of Neurology, Ziv Medical Center, Safed, Israel
- Department of Criminology, Western Galilee College, Acre, Israel
- Issue: Vol 2, No 2 (2020)
- Pages: 48-60
- Section: Biomedical Sciences
- URL: https://journals.eco-vector.com/PharmForm/article/view/34728
- DOI: https://doi.org/10.17816/phf34728
- ID: 34728
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Full Text
Abstract
This study is the proof-of-concept of our "Gravicentric" theory. This concept is based on several fundamental points: obesity as the main foe; rapid reversibility of the disease; as well as a new perspective on the roles different pharmacological classes play in general, and the role of insulin and GLP-1 analogs, in particular. The paper presents and discusses our experience of the implementation of insulin and GLP-1 analogs. The possibility of "insulin weaning"; the therapeutic approach for over-treated patients; and physiological dosing of insulin is also discussed therein.
Objectives
Primary: To evaluate the long-term efficacy of GLP-1 analogs in insulin-treated Type 2 Diabetes Mellitus (T2DM) patients.
Secondary: To analyze which patient would most likely benefit from this combined treatment.
Methods
In 54 T2DM patients with a mean disease duration of 17.5 years and a mean extent of insulin therapy of 4.5 years, additional GLP-1 analogs therapy was prescribed. Mean duration of GLP-1 treatment was 25.8 months (2.15 years).
During the intervention, clinical, biochemical, and anthropometric parameters were analyzed. Compliance, Hypoglycemia and Metabolic Index (MI) assessments were implemented.
Results
Mean Glycated hemoglobin (HbA1C) decreased from 9.28 ± 1.43 to 8.54 ± 1.4% on GLP-1 analogs, p < 0.01. Total Daily dose of Insulin (TDI) showed considerable reduction: 80.6 ± 42.7 U/day before starting GLP-1 vs.41.0 ± 30.7 U/day on GLP-1, p< 0.01. These changes were directly linked to weight loss: BMI has dropped from 35.1 ± 4.8 kg/cm2 before, to 32.8 ± 5.0 kg/cm2 on GLP-1 analogs, with patients losing 6.7 kg on average. Moreover, 13 (24%) participants discontinued at least one kind of insulin, while 7 (13%) stopped taking insulin completely, with simultaneous improvement in diabetes control. No clinically significant hypoglycemia was observed.
Post-hoc, the participants were categorized according to each patient’s ability to reduce TDI by more than 20 U/day, and then split into two groups. Group A – 34 patients (64.2%) who successfully reduced TDI; Group B – 19 patients (35.8%) who failed to do so. The comparison of the two groups showed the following:
- Significantly larger – virtually twice as large – baseline TDI in Group A (97.4±40.4 U/day vs. 52.2±31.0 U/day), p< 0.001.
- Very effective BMI reduction (ΔBMI 3.3 ± 2.4 kg/cm2 0.9 ± 1.2 kg/cm2, p< 0.001) and much better compliance (1.4 ± 1.1 vs. 2.2 ± 1.0, p< 0.02) in Group A.
- A considerable decline of insulin requirements in group A, on GLP-1 therapy (ΔTDI on GLP-1 was -62.4 ± 31.9 U/day) with no TDI reduction in Group “B” (ΔTDI on GLP-1 was +0.03 ± 14.1 U/day, p< 0.001).
Thus, in spite of the fact that on GLP1 therapy HbA1C has declined to the same levels in both groups, patients from group A became much leaner and metabolically healthier.
We suggest overtreatment as the critical factor of obesity in Group A.
Conclusions
Adding GLP-1 analogs to insulin in poorly controlled, insulin-treated T2DM patients resulted in an impressive weight (BMI) reduction with significant improvements in glucose control. This provided for a further decline in insulin resistance and insulin requirements. We suggest that the best candidate for successful GLP-1 analogs therapy is an obese, overtreated and compliant T2DM person. Changes in Metabolic Index (MI) rather than surrogate glycemic parameters (HbA1C) are better predictors of a successful T2DM therapy. Neither the duration of diabetes nor the length of insulin therapy in the past is likely to have a critical role in predicting success. These findings are proof-of-concept of our Gravicentric theory in T2DM.
About the authors
Shmuel levit
Endocrinology and Diabetology Institute affiliated to Assuta Medical Center, Tel Aviv, Israel; Kazan National Research Technological University, Kazan, Russia
Author for correspondence.
Email: prof@levitsh.co.il
ORCID iD: 0000-0003-0406-8021
Доктор медицинских наук, профессор, заведующий НИИ эндокринологии, диабета и метаболизма, медицинский центр "Ассута"; профессор Казанского национального исследовательского технологического университета, Российская Федерация
IsraelNaum Torban
Institute of Endocrinology, Diabetes & Metabolism, Assuta Medical Center, Tel Aviv, Israel
Email: drtorban@levitsh.co.il
ORCID iD: 0000-0001-8891-1711
MD, endocrinologist
Israel, ул. ул. Ха-Нехошет, 10, Тель-Авив 6971028, ИзраильMona Boaz
Department of Nutrition, School of Health Sciences, Ariel University Ariel, Israel; Epidemiology and Research Unit, E. Wolfson Medical Center, Holon, Israel
Email: mboaz8@yahoo.com
ORCID iD: 0000-0002-3920-7549
Ph.D., Professor, Department of Nutrition
IsraelMaria Weichman
Maccabi Health Foundation, Petah – Tiqwa, Israel
Email: mariahdiet@gmail.com
ORCID iD: 0000-0002-9822-8489
Specialist in clinical dietology
IsraelJoseph Azuri
Maccabi Healthcare Services; Lecturer of Sackler Faculty of Medicine, Tel Aviv, Israel
Email: Azuri_yo@mac.org.il
ORCID iD: 0000-0003-1049-9848
MD, Specialist in Family medicine, a member of the research department
Israel
Yossi Manisterski
Maccabi Health Foundation; Petah – Tiqwa, Israel
Email: manister_y@mac.org.il
ORCID iD: 0000-0002-7420-6875
MD, Director of Institute of Diabetes
IsraelEugene Merzon
Leumit Health Foundation, Tel Aviv, Israel; Lecturer of Sackler Faculty of Medicine, Tel Aviv, Israel
Email: emarzon@leumit.co.il
ORCID iD: 0000-0001-5469-0236
MD, Director of Diabetes service, Lecturer of Sackler Faculty of Medicine
IsraelDarian Ryder
Endocrinology and Diabetology Institute affiliated to Assuta Medical Center, Tel Aviv, Israel
Email: Darian@Neurologit.com
ORCID iD: 0000-0001-9691-7136
PhD, Senior Data Scientist
IsraelGideon Ginossar
Urgent Care Consultant the Royal London Hospital, A&E and Urgent Care Centre, London, United Kingdom
Email: Ginossarg@gmail.com
ORCID iD: 0000-0003-2193-6230
MD, Senior physician
United KingdomTali Gavra
Assuta Medical Centers, Tel Aviv University, Tel Aviv, Israel
Email: talig@assuta.co.il
ORCID iD: 0000-0003-2938-2682
Research Unit Director
IsraelVyacheslav Levit
City Clinical Hospital No8, Chelyabinsk, Russia
Email: slava_levit@mail.ru
ORCID iD: 0000-0003-1306-1374
MD, Head of Disease Prevention Department
Russian FederationIvan Domuschiev
Multiprofile Hospital for active treatment “St. Panteleimont”, Sofia, Bulgaria
Email: vopsi@abv.bg
ORCID iD: 0000-0002-7885-0668
MD, Specialist endocrinologist
BulgariaIldar Musin
Kazan National Research Technological University, Kazan, Russia
Email: ildarmusin@mail.ru
ORCID iD: 0000-0003-4516-4183
Scopus Author ID: 57193350975
ResearcherId: V-3175-2017
PhD of Engineering Science, Head of the Department of medical Informatics
Russian FederationChen Hanna Ryder
Department of Neurology, Ziv Medical Center, Safed, Israel; Department of Criminology, Western Galilee College, Acre, Israel
Email: chenryder1@gmail.com
ORCID iD: 0000-0002-9028-1154
PhD, Principal Investigator, Lecturer and Researcher
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