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1.
Obes Surg ; 34(5): 1653-1664, 2024 May.
Article in English | MEDLINE | ID: mdl-38502519

ABSTRACT

BACKGROUND: A significant number of patients face the issue of weight gain (WG) or inadequate weight loss (IWL) post-bariatric surgery for obesity. Several studies have been published evaluating the role of glucagon-like peptide-1 receptor agonists (GLP1RA) for weight loss post-bariatric surgery. However, no systematic review and meta-analysis (SRM) till date has evaluated the efficacy, safety and tolerability of GLP1RA in this clinical scenario. Hence, this SRM aimed to address this knowledge gap. METHODS: Databases were searched for randomized controlled trials (RCTs), case-control, cohort and observational studies involving use of GLP1RA in the intervention arm post-bariatric surgery. Primary outcome was weight loss post at least 3 months of therapy. Secondary outcomes were evaluation of body composition parameters, total adverse events (TAEs) and severe adverse events (SAEs). RESULTS: From initially screened 1759 articles, 8 studies (557 individuals) were analysed. Compared to placebo, patients receiving liraglutide had significantly greater weight loss after 6-month therapy [MD - 6.0 kg (95% CI, - 8.66 to - 3.33); P < 0.001; I2 = 79%]. Compared to liraglutide, semaglutide had significantly greater percent reduction in body weight after 6-month [MD - 2.57% (95% CI, - 3.91 to - 1.23); P < 0.001; I2 = 0%] and 12-month [MD - 4.15% (95% CI, - 6.96 to - 1.34); P = 0.004] therapy. In study by Murvelashvili et al. (2023), after 12-month therapy, semaglutide had significantly higher rates of achieving > 15% [OR 2.15 (95% CI, 1.07-4.33); P = 0.03; n = 207] and > 10% [OR 2.10 (95% CI, 1.19-3.71); P = 0.01; n = 207] weight loss. A significant decrease in fat mass [MD - 4.78 kg (95% CI, - 7.11 to - 2.45); P < 0.001], lean mass [MD - 3.01 kg (95% CI, - 4.80 to - 1.22); P = 0.001] and whole-body bone mineral density [MD - 0.02 kg/m2 (95% CI, - 0.04 to - 0.00); P = 0.03] was noted with liraglutide. CONCLUSION: Current data is encouraging regarding use of GLP1RAs for managing WG or IWL post-bariatric surgery. Deterioration of bone health and muscle mass remains a concern needing further evaluation. TRIAL REGISTRATION: The predefined protocol has been registered in PROSPERO having registration number of CRD42023473991.


Subject(s)
Bariatric Surgery , Diabetes Mellitus, Type 2 , Obesity, Morbid , Humans , Liraglutide/pharmacology , Liraglutide/therapeutic use , Glucagon-Like Peptide-1 Receptor Agonists , Obesity, Morbid/surgery , Weight Loss , Hypoglycemic Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/surgery
2.
World J Clin Cases ; 12(1): 9-14, 2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38292619

ABSTRACT

The knowledge of the pathogenesis of type 1 diabetes mellitus (T1DM) continues to rapidly evolve. The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status. Not all individuals of T1DM progress in that specific sequence. We hereby present a case of T1DM with a classical third phase (honeymoon phase) and discuss the intricacies of this interesting phase along with a possible future promise of "cure" with the use of immunotherapies. We now know that the course of T1DM may not be in only one direction towards further progression; rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed. The third phase popularly called the "honeymoon phase", is of special interest as this phase is complex in its pathogenesis. The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive "diabetes reversal" in T1DM. Identifying this phase is therefore the key, with a lot of varying criteria having been proposed.

3.
World J Diabetes ; 14(3): 347-351, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-37035224

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a lifelong condition and a grave threat to human health. Innovative efforts to relieve its detrimental effects are acutely needed. The sine qua non in T2DM management is consistent adherence to a prudent lifestyle and nutrition, combined with aerobic and resistance exercise regimens, together repeatedly shown to lead to complete reversal and even long-term remission. Non-adherence to the above lifestyle adjustments condemns any treatment effort and ultimately the patient to a grim fate. It is thus imperative that every study evaluating the effects of innovative interventions in T2DM objectively compares the novel treatment modality to lifestyle modifications, preferably through double-blind controlled randomization, before claiming efficacy.

4.
Nutrients ; 14(24)2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36558484

ABSTRACT

Effective nutrition therapy is a pressing issue in obesity and type 2 diabetes mellitus (T2DM) management. As such, this research aimed to determine the performance of a revised dietary strategy built on the protein-sparing diet in obesity and type 2 diabetes mellitus with regard to obtaining a rapid and stable improvement in glucometabolic control, body weight, body composition, and energy metabolism when applying the strategy in just twenty-one days. The revised protein-sparing diet differs from the traditional protein-sparing modified fast (PSMF) because it does not include foods. The daily calorie intake of this diet is exclusively derived from Isolate whey protein in addition to a formulation of Isolate whey protein enriched with essential amino acids in free form, with the addition of lipids such as extra virgin olive oil and coconut oil as a source of medium chain fatty acids, where the latter is taken for only the first four days of the diet, together with the use, for the same duration, of extended-release metformin, as the only antihyperglycemic allowed. Anthropometric measurements, bioimpedance analysis, indirect calorimetry, and blood chemistry assessments were conducted at the beginning of the study, time 0 (T0), and at the end, time 1 (T1), i.e., on the 21st day. The main outcomes of the revised protein-sparing diet after only twenty-one days were a reduction in body weight with the predominant loss of visceral atherogenic abdominal fat and, therefore, a possible contextual reduction in ectopic fat deposits together with a simultaneous reduction in insulin resistance and normalization of insulin levels, maintenance of free fat mass and basal metabolism, restoration of metabolic flexibility, and improvement of the glucometabolic and lipidic parameters. These results demonstrate the promising potential of the revised protein-sparing diet as an "etiologic tool" in the integrated nutritional treatment of metabolic diseases such as obesity and type 2 diabetes mellitus.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/metabolism , Whey Proteins , Obesity , Body Weight , Diet
5.
BMC Endocr Disord ; 22(1): 290, 2022 Nov 22.
Article in English | MEDLINE | ID: mdl-36419152

ABSTRACT

BACKGROUND: Type 2 diabetes (T2D) is a chronic, progressive lifestyle disease and the most rapidly growing health challenge of the twenty-first century. The American Diabetes Association recommends that T2D reversal can be achieved through an organized, and systematic approach focusing on nutrition, fitness, and lifestyle management. AIM: This study aimed to evaluate the effectiveness of a comprehensive and multi-interventional diabetes care program called Sugar. Fit Diabetes Reversal Programme (SDRP) on glycosylated haemoglobin (HbA1c), fasting blood sugar (FBS), and body weight for T2D reversal. METHODOLOGY: SDRP is a personalized intervention study that uses technology-enabled medical management, dedicated coach-led diabetes, and nutrition experts. The study involved 150 patients living with type 2 diabetes in the age group of 20 to 80 years and having HbA1c of > 6.5%. In SDRP, the participants were assigned personal medical doctors specializing in diabetes, along with health coaches for providing customized nutrition, personalized fitness routines, relevant lifestyle modifications to holistically reverse type 2 diabetes. The HbA1c level, fasting blood sugar, and weight of the participants were measured at baseline and the end of the study (90th day). The effectiveness of SDRP was analyzed by comparing it with a control group that involved 110 individuals with type 2 diabetes managed by conventional pharmacotherapy and regular dietary advice but not participating in the SDRP. RESULTS: All 150 participants adhered to the program for 90 days. The analysis was performed on participants and represented as mean ± standard deviation (mean ± SD). At the end of SDRP, a significant reduction in HbA1c level, FBS, and weight was observed as compared to the control group. The results showed that Hba1c levels dropped from 9.0 ± 1.5% to 7.1 ± 1.3% with a mean change of 1.9 ± 1.5%; FBS levels decreased from 178.3 ± 57.1 mg/dL to 116.1 ± 24.2 mg/dL with a mean loss of 62.2 ± 51.8 mg/dL, and the weight decreased from 76.7 ± 12.7 kg to 73.8 ± 11.8 kg with a mean weight loss of 2.8 ± 1.6 kg. The results also showed that participants between 20 to 35 years showed the highest drop in HbA1c, FBS, and weight. CONCLUSION: The findings indicate that a comprehensive and multi-interventional diabetes care program involving personalized nutrition, fitness, and lifestyle modification such as SDRP, help in significant and sustained improvements in HbA1c level, glycaemic control, and weight loss in adults with type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Adult , Humans , Young Adult , Middle Aged , Aged , Aged, 80 and over , Glycated Hemoglobin/analysis , Blood Glucose , Retrospective Studies , Fasting , Life Style , Weight Loss
6.
Vasc Health Risk Manag ; 18: 417-443, 2022.
Article in English | MEDLINE | ID: mdl-35726218

ABSTRACT

Over the past 50 years, many countries around the world have faced an unchecked pandemic of obesity and type 2 diabetes (T2DM). As best practice treatment of T2DM has done very little to check its growth, the pandemic of diabesity now threatens to make health-care systems economically more difficult for governments and individuals to manage within their budgets. The conventional view has been that T2DM is irreversible and progressive. However, in 2016, the World Health Organization (WHO) global report on diabetes added for the first time a section on diabetes reversal and acknowledged that it could be achieved through a number of therapeutic approaches. Many studies indicate that diabetes reversal, and possibly even long-term remission, is achievable, belying the conventional view. However, T2DM reversal is not yet a standardized area of practice and some questions remain about long-term outcomes. Diabetes reversal through diet is not articulated or discussed as a first-line target (or even goal) of treatment by any internationally recognized guidelines, which are mostly silent on the topic beyond encouraging lifestyle interventions in general. This review paper examines all the sustainable, practical, and scalable approaches to T2DM reversal, highlighting the evidence base, and serves as an interim update for practitioners looking to fill the practical knowledge gap on this topic in conventional diabetes guidelines.


Subject(s)
Bariatric Surgery , Diabetes Mellitus, Type 2 , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Humans , Life Style , Obesity , Treatment Outcome
7.
Ann Afr Med ; 21(1): 26-33, 2022.
Article in English | MEDLINE | ID: mdl-35313401

ABSTRACT

Background: Costs are important cause of therapeutic noncompliance in type-2 diabetes mellitus (T2DM). Half-tablet empagliflozin (EMPA)-25 mg has lowest monthly cost among all EMPA preparations; data is unavailable on efficacy of half EMPA-25. This study compared real world weight loss and glycaemic outcomes of 10 mg versus 12.5 mg versus 25 mg of EMPA. Methods: Data, retrospectively captured from records of 2 different centresfor patients > 35 years-age having T2DM on EMPA as part of standard pharmacotherapy for T2DM, having > 6 months follow-up data available was analysed. Patients were in 3-groups depending on EMPA dosage: Group 1 on EMPA 10 mg/day (1-tablet EMPA-10), Group-2 on EMPA 12.5 mg/day (half-tablet EMPA-25), and Group 3 on EMPA 25 mg/day (1-tablet EMPA-25). Primary endpoints were glycaemic efficacy and weight-loss. Results: Of 3601 records screened, data from 599 patients (184, 239 and 176 in Group-1, 2 and 3 respectively) was analysed. All 3 groups were comparable with regards to sex, blood pressure, haemoglobin, renal function, medications use. Group-3 were significantly older, had longest diabetes duration, highest HbA1c and lowest body mass index. Glycaemic efficacy was comparable among groups (ΔHbA1c Groups 1-3: -0.9 (-1.9 - 0.0), -1.0 (-1.8 - 0.5) and - 1.0 (-1.5 - 0.22], respectively; P = 0.363). Patients on EMPA 12.5 or 25 mg/d had significantly higher total (-1.4 [-3.0 -0.2] vs. -0.3 [-2.4 - 1.32] kg; P = 0.028) and percent weight-loss (-1.75% [-4.15 - 0.26] vs. -0.44% [-3.11 - 1.39]; P = 0.039), and significantly higherfraction achieving HbA1c < 5.7% (12% vs. 0; P = 0.021), compared to EMPA-10. Conclusion: Half EMPA-25 is the most cost effective way of using EMPA in clinical practice.


Résumé Contexte: Les coûts sont une cause importante de non-conformité thérapeutique dans le diabète sucré de type 2 (DT2). Empagliflozine demi-comprimé (EMPA) -25 mg a le coût mensuel le plus bas parmi toutes les préparations EMPA; les données ne sont pas disponibles sur l'efficacité de la moitié de l'EMPA-25. Cette étude a comparé le monde réel perte de poids et résultats glycémiques de 10 mg contre 12,5 mg contre 25 mg d'EMPA. Méthodes: Données, capturées rétrospectivement à partir d'enregistrements de 2 centres différents pour les patients de plus de 35 ans ayant un DT2 sous AEM dans le cadre de la pharmacothérapie standard pour le DT2, ayant> 6 mois les données de suivi disponibles ont été analysées. Les patients étaient répartis en 3 groupes en fonction de la posologie d'EMPA: Groupe 1 sous EMPA 10 mg / jour (1 comprimé d'EMPA-10), Groupe-2 sur EMPA 12,5 mg / jour (demi-comprimé EMPA-25) et groupe 3 sur EMPA 25 mg / jour (1 comprimé EMPA-25). Les critères d'évaluation principaux étaient glycémiques efficacité et perte de poids. Résultats: sur 3601 enregistrements examinés, les données de 599 patients (184, 239 et 176 dans les groupes 1, 2 et 3 respectivement) étaient analysé. Les 3 groupes étaient comparables en ce qui concerne le sexe, la pression artérielle, l'hémoglobine, la fonction rénale et l'utilisation de médicaments. Groupe-3 étaient significativement plus âgé, avait la plus longue durée de diabète, le plus haut taux d'HbA1c et le plus bas indice de masse corporelle L'efficacité glycémique était comparable entre groupes (ΔHbA1c Groupes 1 à 3: −0,9 (−1,9 - 0,0), −1,0 (−1,8 - 0,5) et - 1,0 (−1,5 - 0,22], respectivement; P = 0,363). Patients sous EMPA 12,5 ou 25 mg / j avaient un total significativement plus élevé (−1,4 [−3,0 ­0,2] contre −0,3 [−2,4 - 1,32] kg; P = 0,028) et un pourcentage de perte de poids (−1,75% [−4,15 - 0,26] contre −0,44% [−3,11 - 1,39]; P = 0,039), et une fraction significativement plus élevée atteignant un taux d'HbA1c <5,7% (12% contre 0; P = 0,021), par rapport à EMPA-10. Conclusion: HalfEMPA-25 est le moyen le plus rentable d'utiliser EMPA dans la pratique clinique. Mots-clés: Diabésité, inversion du diabète, empagliflozine, euglycémie, perte de poids.


Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Benzhydryl Compounds , Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Glucosides , Glycated Hemoglobin , Humans , Hypoglycemic Agents/therapeutic use , Infant , Retrospective Studies , Treatment Outcome
8.
Diabetes Metab Syndr ; 16(4): 102452, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35306265

ABSTRACT

BACKGROUND AND AIM: The field of diabetes reversal is continuously evolving. Strategies for implementing diabetes care towards diabetes reversal are still being worked out. We aim to analyse data from available literature to ascertain factors allowing patient centric dietary approach to achieve diabetes reversal in clinical practice. METHODS: In this exploratory review, an update on current knowledge is presented to delineate factors driving diabetes remission in an individual based on major studies in the field. This knowledge is then applied to subtypes of type 2 diabetes to optimise dietary approach for reversal of diabetes. RESULTS AND CONCLUSION: Shorter duration of diabetes, lesser number of medicines needed to achieve euglycemia and 15 kg weight loss are common factors favouring diabetes remission in all major studies. A patient centric approach to diabetes reversal taking into account the recently described diabetes subtypes is being proposed to improve the proportion of patients achieving remission. We also propose the parameters of a novel diabetes remission prediction score, based on patient motivation, interaction with the care-team, level of diabetes self-care and the intent of the care-team.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes Mellitus, Type 2/therapy , Diet , Humans , Remission Induction , Weight Loss
9.
Clin Diabetes Endocrinol ; 7(1): 21, 2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34776010

ABSTRACT

BACKGROUND: Type 2 diabetes reversal has been viewed in the literature primarily as a dichotomous event (reversed or not reversed), even though this viewpoint may not be optimal for clinicians or patients. This cohort study's objectives were to define stages of type 2 diabetes reversal and measure changes in reversal stages before and after 90 days of digital twin-enabled precision nutrition therapy. METHODS: This study defines seven stages of diabetes reversal. The study is a retrospective pre/post comparison of changes in reversal stage, hemoglobin A1c (HbA1c), weight, body mass index (BMI), and other metrics measured before and after precision nutrition therapy. Reversal stages were defined as Stage 0: HbA1c < 5.7% without medication for > 1 year, Stage 1: HbA1c < 5.7% without medication for < 1 year, Stage 2: HbA1c < 6.5% without medication, Stage 3: estimated HbA1c (eA1c) between 5.7 and 6.4% without medication, Stage 4: estimated HbA1c (eA1c) between 5.7 and 6.4% with metformin monotherapy, Stage 5: dual oral therapy, Stage 6: > = 3 medications. RESULTS: Reversal stage information was available for 463 patients at baseline and 90 days. At baseline, the proportions of patients in each reversal stage were Stages 1 and 2: 0%, Stage 3: 1%, Stage 4: 8%, Stage 5: 6%, and Stage 6: 85%. After 90 days, the proportions in each reversal stage were Stage 1: 2%, Stage 2: 9%, Stage 3: 32%, Stage 4: 39%, Stage 5: 7%, and Stage 6: 11%, indicating significant progress. Reversal stage progression rates varied by patient subgroup. CONCLUSIONS: Type 2 diabetes patients reached differing reversal stages during 90 days of precision nutrition therapy. Use of reversal stages may benefit patients during therapy. TRIAL REGISTRATION: This was a retrospective study that was approved by the Medisys Clinisearch Ethical Review Board (without registration number) in 2019.

10.
Front Immunol ; 12: 667897, 2021.
Article in English | MEDLINE | ID: mdl-34108968

ABSTRACT

A therapy that includes an oral vaccine for type 1 diabetes (T1D) using live attenuated Salmonella MvP728 (ΔhtrA/ΔpurD), cytokines (IL10 and TGFß) and preproinsulin (PPI) antigen in combination with a sub-therapeutic dose of anti-CD3 mAb was developed by our team. The vaccine combination therapy reduced insulitis and prevented and reversed diabetes in non-obese diabetic (NOD) mice. Here, we show the effectiveness of an alternative Salmonella mutant (ΔmsbB) as a carrier strain, which is anticipated to have lower risks of an inflammatory response and septicemia as a result of modification in the lipopolysaccharide (LPS) via detoxification of lipid A. This mutant strain proved to have highly reduced pathogenic side effects. Salmonella strain ΔmsbB expressed autoantigens and in combination with cytokines and anti-CD3 mAb, successfully prevented and reversed T1D to levels comparable to the previously used carrier strain ΔhtrA/ΔpurD. Additionally, the Salmonella msbB mutant resulted in higher rates of host cell infection. These results further demonstrate the potential of an oral Salmonella-based combined therapy in the treatment of early T1D.


Subject(s)
Acyltransferases/genetics , Bacterial Proteins/genetics , Blood Glucose/metabolism , Diabetes Mellitus, Type 1/prevention & control , Genetic Vectors , Mutation , Salmonella/genetics , Vaccines, DNA/administration & dosage , Administration, Oral , Animals , Antibodies, Monoclonal/administration & dosage , Biomarkers/blood , CD3 Complex/antagonists & inhibitors , CD3 Complex/immunology , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/immunology , Disease Models, Animal , Female , Insulin/administration & dosage , Insulin/genetics , Interleukin-10/administration & dosage , Interleukin-10/genetics , Mice , Mice, Inbred NOD , Protein Precursors/administration & dosage , Protein Precursors/genetics , RAW 264.7 Cells , Salmonella/immunology , Salmonella/pathogenicity , Transforming Growth Factor beta1/administration & dosage , Transforming Growth Factor beta1/genetics , Vaccines, Attenuated/administration & dosage , Vaccines, DNA/genetics , Vaccines, DNA/immunology
11.
Indian J Endocrinol Metab ; 25(4): 342-347, 2021.
Article in English | MEDLINE | ID: mdl-35136743

ABSTRACT

CONTEXT: Diabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent and reduce the risk of long-term complications. It requires an array of investigations to provide an accurate picture of the condition and its management accordingly by a qualified doctor. AIMS: This study was conducted to understand the treatment received by type 2 diabetes (T2DM) patients from various categories of health care professionals and awareness about diabetes reversal by lifestyle modification and prevention of complications. SETTINGS AND DESIGN: This was a community-based cross-sectional study. SUBJECTS AND METHODS: The link of the semi-structured questionnaire in Google form with e-consent was sent to all members in the selected groups of "World free of obesity and diabetes" campaign on their personal WhatsApp account. STATISTICAL ANALYSIS USED: A total of 3082 participants were included, and the data obtained were analyzed using SPSS v26. RESULTS: The mean age of the participants was 50.26 ± 9.78 years ranging from 18 to 81 years. A total of 35.8% of the study population was diabetic for 1-5 years. A total of 54.9% were started with antidiabetic medication on the same day of diagnosis. Only 1.5% of the patients had complete investigation profile for T2DM, 50.2% of the patients were briefed about hypoglycemia, and only 15.8% of the patients were checked for retinopathy. CONCLUSIONS: Most doctors, qualified as well as nonqualified, did not follow the standard guidelines for diagnosis, treatment, and patient education regarding T2DM; therefore, it is necessary to train all medical practitioners regarding these guidelines. Diabetes reversal by lifestyle modification must be prescribed as the first line of treatment in patients with T2DM.

12.
Diabetologia ; 63(5): 987-1001, 2020 05.
Article in English | MEDLINE | ID: mdl-32072192

ABSTRACT

AIMS/HYPOTHESIS: High-mobility group box 1 (HMGB1), an evolutionarily conserved chromosomal protein, was rediscovered to be a 'danger signal' (alarmin) that alerts the immune system once released extracellularly. Therefore, it has been recognised contributing to the pathogenesis of autoimmune diabetes, but its exact impact on the initiation and progression of type 1 diabetes, as well as the related molecular mechanisms, are yet to be fully characterised. METHODS: In the current report, we employed NOD mice as a model to dissect the impact of blocking HMGB1 on the prevention, treatment and reversal of type 1 diabetes. To study the mechanism involved, we extensively examined the characteristics of regulatory T cells (Tregs) and their related signalling pathways upon HMGB1 stimulation. Furthermore, we investigated the relevance of our data to human autoimmune diabetes. RESULTS: Neutralising HMGB1 both delayed diabetes onset and, of particular relevance, reversed diabetes in 13 out of 20 new-onset diabetic NOD mice. Consistently, blockade of HMGB1 prevented islet isografts from autoimmune attack in diabetic NOD mice. Using transgenic reporter mice that carry a Foxp3 lineage reporter construct, we found that administration of HMGB1 impairs Treg stability and function. Mechanistic studies revealed that HMGB1 activates receptor for AGE (RAGE) and toll-like receptor (TLR)4 to enhance phosphatidylinositol 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) signalling, thereby impairing Treg stability and functionality. Indeed, high circulating levels of HMGB1 in human participants with type 1 diabetes contribute to Treg instability, suggesting that blockade of HMGB1 could be an effective therapy against type 1 diabetes in clinical settings. CONCLUSIONS/INTERPRETATION: The present data support the possibility that HMGB1 could be a viable therapeutic target to prevent the initiation, progression and recurrence of autoimmunity in the setting of type 1 diabetes.


Subject(s)
Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/metabolism , HMGB1 Protein/metabolism , T-Lymphocytes, Regulatory/metabolism , Animals , Antibodies, Neutralizing/pharmacology , Blotting, Western , Cells, Cultured , Colitis/immunology , Colitis/metabolism , Colitis/pathology , Diabetes Mellitus, Type 1/pathology , Female , HMGB1 Protein/antagonists & inhibitors , Humans , Islets of Langerhans Transplantation , Mice , Mice, Inbred BALB C , Mice, Inbred NOD , Phosphatidylinositol 3-Kinases/metabolism
13.
Indian J Endocrinol Metab ; 23(4): 460-467, 2019.
Article in English | MEDLINE | ID: mdl-31741907

ABSTRACT

BACKGROUND: This study evaluated the real-world weight loss and glycemic outcomes of multidrug therapy (MDT) according to various combinations of metformin, sodium-glucose cotransporter -2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor analogs (GLP1a), and orlistat in diabesity. METHODS: Data retrospectively captured from medical records of 2 different centers in New Delhi for patients >35 years-age having prediabetes/diabetes and on at least any one of the 4 above medications with >6-months follow-up was analyzed. RESULTS: In total, 5,336 patient records were screened; 2,442 with prediabetes/diabetes were considered; 1,509 patients who fulfilled all criteria were analyzed. Use of metformin, SGLT2i, sulfonylureas, DPP4i, pioglitazone, orlistat, and GLP1a was 85.35%, 74.95%, 68.32%, 60%, 39.16%, 9.08%, and 4.17%, respectively. However, 365, 970, and 104 patients were on one of 4 concerned medications (Group-1; 24.18%), dual MDT (Group-2; 64.28%), and triple/quadruple MDT (Group-3; 6.89%). Metformin with SGLT2i was most commonly used dual MDT (94.12%). Analysis according to weight-loss quartiles from 558 patients showed 6.9 kg weight-loss in the highest quartile. People losing maximum weight were significantly younger; had higher use of metformin, SGLT2i, GLP1, orlistat, and lower pioglitazone use; greatest HbA1c reduction (-1.3 vs. -0.3; quartile-1 vs. quartile -4; P < 0.001); and significantly higher occurrence of HbA1c<5.7% (16.8% vs. 6.29%; quartile-1 vs. 4; P < 0.001). Patients in Group-3 had the highest baseline BMI and maximum weight loss with highest number of patients with HbA1c<5.7% (19.44% vs. 10.34%; Group-3 vs. Group-1; P < 0.001). CONCLUSION: Greater weight loss with HbA1c reduction along with a greater number of patients attaining HbA1c <5.7% highlights that MDT is the way forward to tackle diabesity in India.

14.
Nutrients ; 11(4)2019 Apr 01.
Article in English | MEDLINE | ID: mdl-30939855

ABSTRACT

BACKGROUND: Type 2 diabetes (T2D) has long been identified as an incurable chronic disease based on traditional means of treatment. Research now exists that suggests reversal is possible through other means that have only recently been embraced in the guidelines. This narrative review examines the evidence for T2D reversal using each of the three methods, including advantages and limitations for each. METHODS: A literature search was performed, and a total of 99 original articles containing information pertaining to diabetes reversal or remission were included. RESULTS: Evidence exists that T2D reversal is achievable using bariatric surgery, low-calorie diets (LCD), or carbohydrate restriction (LC). Bariatric surgery has been recommended for the treatment of T2D since 2016 by an international diabetes consensus group. Both the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) now recommend a LC eating pattern and support the short-term use of LCD for weight loss. However, only T2D treatment, not reversal, is discussed in their guidelines. CONCLUSION: Given the state of evidence for T2D reversal, healthcare providers need to be educated on reversal options so they can actively engage in counseling patients who may desire this approach to their disease.


Subject(s)
Bariatric Surgery , Caloric Restriction , Diabetes Mellitus, Type 2/therapy , Diet, Carbohydrate-Restricted , Europe , Humans , Weight Loss
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