Type 2 diabetes therapeutic strategies: why don't we see the «ELEPHANT» in the room?

Levit, Shmuel; Giveon, Shmuel; Philippov, Yury I.; Domuschiev, Ivan; Zivony, Amir

doi:10.14341/dm7077

Cited by 6 publications

(8 citation statements)

References 30 publications

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“…Insulin is widely used for this aim in modern clinical practice but many questions remain to be answered about the negative side effect of insulin action. One of them is diabetes relapse in patients with growing weight due to insulin-stimulated fat accumulation [ 44 ]. This clinical observation complies well with the model that is presented in the graphic abstract.…”

Section: Catabolic Shift In Prediabetic State As Target For Therapeutmentioning

confidence: 99%

Catabolic and Anabolic Faces of Insulin Resistance and their Disorders: A New Insight into Circadian Control of Metabolic Disorders Leading to Diabetes

Schwartsburd

2017

Future Sci. OA

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Maintenance of glucose homeostasis during circadian behavioral cycles is critical. The processes controlling the switch between predominant lipolysis/fatty oxidation during fasting and predominant lipid storage/glucose oxidation following feeding are determined principally by insulin. Chronic elevated threshold of insulin resistance (IR) is a key pathological feature of obesity, Type 2 diabetes, sepsis and cancer cachexia; however, a temporal reduced threshold of IR is widely met in fasting/hibernation, pregnancy, antibacterial immunity, exercise and stress. Paradoxically, some of these cases are associated with catabolic metabolism, whereas others are related to anabolic pathways. This article considers the possible causes of circadian disorders in glucose and lipid metabolism that act as a driving force for obesity-promoted development of Type 2 diabetes. This is intended to provide improved insight into the pathogenesis of chronic circadian disorders that increase the risk of diabetes, and consider new targets for its metabolic and drug correction.

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Section: Catabolic Shift In Prediabetic State As Target For Therapeutmentioning

confidence: 99%

Catabolic and Anabolic Faces of Insulin Resistance and their Disorders: A New Insight into Circadian Control of Metabolic Disorders Leading to Diabetes

Schwartsburd

2017

Future Sci. OA

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“…Of note, Insulin was subsequently withdrawn in ten patients (19.2%), whose glycemic control remained excellent, in full accordance to our de-intensification approach. [21]…”

Section: Resultsmentioning

confidence: 99%

“…All study participants were treated according to our energetic (Gravicentric) concept and algorithm, [20][21][22] where patient's weight reduction is of the highest priority.…”

Section: Discussionmentioning

confidence: 99%

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Continuous glucose monitoring - proved hypoglycemia in sodium-glucose co-transporter-2 inhibitors - treated type 2 diabetes patients: a link to ketosis development

et al. 2019

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Background: Latest studies have shown the remarkable ability of sodium-glucose co-transporter-2 inhibitors (SGLT2i) to reduce cardiovascular morbidity and mortality. However, real-life data and the results of several other studies seem to contradict these outcomes, pointing out possibilities of serious side effects. Ketoacidosis (KA) remains one of the most dangerous complications, yet, not fully understood. All of the above urgently requires real-practice data, which may shed some light on side effects of this novel anti-diabetic drug family. Aims: To investigate the real-life rates of hypoglycemia and ketosis (K) in SGLT2i treated patients, using Continuous Glucose Monitoring (CGM) and capillary blood -hydroxybutyrate measurements. Methods: We report the results of a two-year retrospective analysis of 136 Type 2 Diabetes (T2DM) patients, all (100%) treated with a SGLT2i, combined with Metformin or Metformin with Incretin-Based therapy (MT-IBT). CGM recordings were done in 52 persons. In 9 patients (Group A), CGM-proved hypoglycemic episodes were discovered. The rest of 43 patients (Group B) didnt show any hypoglycemia. Three patients in Group A and 11 from Group B were also treated with small doses of basal insulin on admission; the insulin was later discontinued in all patients of Group A and seven patients of Group B . Main characteristics of two groups were subsequently compared. Results: CGM data analysis showed significantly lower average Sensor Glucose (SG) , 7.21.3 vs. 8.21.7 mmol/l, p=0.04, and estimated HbA1c , 6.10.7 vs. 6.81.1%, p=0.02, in Group A patients. We also report three cases of ketosis, proved by elevated capillary -hydroxybutyrate concentrations. Pathophysiological link between frequent hypoglycemia rates (Six patients without insulin treatment (11.5 % in total CGM group of 52 patients)) and ketosis development (Three patients (2.2% in total cohort of 136 participants)) was suggested. Conclusions: More frequent than previously reported rates of hypoglycemia and ketoacidosis were discovered in patients taking SGLT2 inhibitors. Pathophysiological link between the two conditions is assumed. More studies are needed to confirm our hypothesis.

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“…We have recently proposed an energetic (Gravicentric) concept of T2DM pathogenesis and therapy [11,12]. This concept is key to a better understanding of the underlying processes in T2DM and allows us to revise the traditional (Glucocentric) approach to the perception and therapy of the disease.…”

Section: Introductionmentioning

confidence: 99%

Gravicentric approach to Type 2 Diabetes therapy. The success prediction. A proof-of-concept

et al. 2020

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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 patients 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 (97.440.4 U/day vs. 52.231.0 U/day), p 0.001. Very effective BMI reduction (BMI 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 (TDI on GLP-1 was -62.4 31.9 U/day) with no TDI reduction in Group B (TDI 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.

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Type 2 diabetes therapeutic strategies: why don't we see the «ELEPHANT» in the room?

Cited by 6 publications

References 30 publications

Catabolic and Anabolic Faces of Insulin Resistance and their Disorders: A New Insight into Circadian Control of Metabolic Disorders Leading to Diabetes

Catabolic and Anabolic Faces of Insulin Resistance and their Disorders: A New Insight into Circadian Control of Metabolic Disorders Leading to Diabetes

Continuous glucose monitoring - proved hypoglycemia in sodium-glucose co-transporter-2 inhibitors - treated type 2 diabetes patients: a link to ketosis development

Gravicentric approach to Type 2 Diabetes therapy. The success prediction. A proof-of-concept

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