BACKGROUND: Previous studies have shown that there are racial disparities in type 2 diabetes (T2DM) remission following bariatric surgery, with African-Americans (AA) in particular experiencing a subsequent relapse. In recent years, some have attributed these findings to racial differences in fasting insulin levels, with AA having higher levels, as increasing evidence for an alternate model of T2DM pathophysiology gains support. In this model, basal hyperinsulinemia is considered a primary event in T2DM disease development, rather than a compensatory response to increased insulin resistance. This study aimed to compare glycemic outcomes after bariatric surgery in different races, namely African-Americans (AA), Hispanic-Americans (HA), and Caucasian-Americans (CA), and to determine whether there were any associated changes in insulin levels and insulin resistance that may lend support to this revised model of T2DM pathophysiology. METHODS: A retrospective medical record review of 1,326 patients (389 AA, 179 HA, and 758 CA) who underwent bariatric surgery at Boston Medical Center (BMC) from 2004 to 2015 was conducted. Baseline characteristics and maximum percent weight loss were compared using one-way ANOVA and Chi-square tests of independence. Changes in mean glycated hemoglobin (HbA1c), insulin levels, insulin resistance (HOMA-IR), and blood glucose levels were analyzed using linear mixed models, overall and by racial group. The same procedures were conducted in both the overall patient population and a T2DM subpopulation. RESULTS: Over an 11-year postoperative observation period, all racial groups underwent a significant decrease in HbA1c (P<0.001) within the first two years following surgery. While HbA1c levels remained stable in CA and HA, they began to rise at 2 years in AA only (P=0.043). Additionally, analyses of covariates, including age at surgery (P=0.005), initial BMI (P<0.001), and maximum weight loss (P=0.049), revealed that all three were significant factors affecting mean HbA1c levels. However, when included in the mixed model, the race x time interaction effect on mean HbA1c remained significant. There was also a significant overall decrease in both insulin and HOMA-IR. When stratified by race, analysis of the T2DM population showed that insulin levels began to increase again by the 2nd year after surgery in AA, while in CA and HA they continued to decrease and subsequently stabilize. Analysis of the total patient population showed that HOMA-IR levels in AA, as well as in CA and HA, continued to decrease at this 2-year time point. Decreases in blood glucose levels after surgery were significant overall (P<0.001), but not significant when stratified by race. CONCLUSIONS: After the initial “metabolic reset” that occurs within the first 2 years after bariatric surgery, during which HbA1c levels normalize in the vast majority of patients, it was observed only in the AA population that there was a steady increase in HbA1c to levels near those recorded at baseline. This coincided with an observation of increasing insulin levels despite decreasing insulin resistance seen in AA only. Our results suggest that current discussions regarding a revised model of T2DM pathophysiology, in which hyperinsulinemia precedes insulin resistance, may help explain the racial disparities in glycemic control observed in both post-surgical and non-surgical contexts of T2DM outcome. However, future prospective studies are needed to further the preliminary results of this study.

Introdução: A Doença Hepática Gordurosa Não Alcoólica (DHGNA) tem como causa principal a obesidade. Atualmente não existe tratamento medicamentoso específico para DHGNA. A cirurgia bariátrica surge como uma alternativa de tratamento em pacientes morbidamente obesos. Objetivos: Analisar, através de biópsia hepática intra-operatória, o grau de comprometimento hepático em obesos submetidos à cirurgia bariátrica, correlacionando os achados histopatológicos com o estado glicêmico dos pacientes. Métodos: Estudo de coorte prospectivo incluindo 521 pacientes submetidos à cirurgia bariátrica de julho de 2001 até dezembro de 2016. Os pacientes foram classificados em três grupos de acordo com o status glicêmico basal: 167(32,05%) diabéticos tipo 2 (G1), 132 (25,33%) pré-diabéticos (G2) e 222 (42,61%) obesos normoglicêmicos (G3). Foram obtidas biópsias hepáticas transoperatórias, as quais foram classificadas conforme os critérios de Brunt e do NASH-CRN. As variáveis clínicas e bioquímicas e histológicas foram comparadas antes da cirurgia e durante o seguimento pós-operatório. Resultados: A prevalência de DHGNA nesta coorte foi de 95%. Não houve diferença quanto ao gênero e IMC entre os grupos. Observaram-se taxas mais altas de fibrose (56,4% G1 vs 29,2% G2 vs 28,6% G3 p<0,001) e Esteatohepatite Não Alcoólica (EHNA) (59,4% G1vs 49,2% G2 vs 36% G3 p <0,001) nos pacientes diabéticos. Apenas 1,5 %, dos diabéticos apresentaram histologia normal (vs 7,76% G2 vs 15,7% G3). / Introduction: Obesity is the main cause of nonalcoholic fatty liver disease (NAFLD), for which there is currently no specific medical treatment. Bariatric surgery is a treatment alternative for morbidly obese patients. Objectives: Use an intraoperative liver biopsy to analyze the degree of liver damage in obese patients submitted to bariatric surgery and correlates the histopathological findings with glucose status. Methods: Prospective cohort study of 521 morbid obese patients undergoing bariatric surgery from July 2001 to December 2016, classified into three groups according to their baseline glucose status: 167 (32.05%) type 2 diabetes (G1), 132 (25.33%) pre-diabetic (G2) and 222 (42.61%) normoglycemic obese (G3). Patients using potentially hepatotoxic medications and a history of ethanol consumption or viral hepatitis were excluded. Intraoperative liver biopsies were obtained and classified in accordance with Brunt and NASH-CRN criteria. Clinical, biochemical and histopathological variables were compared before surgery and during postoperative follow-up. Results: The prevalence NAFLD was 95%. There was no intergroup difference for sex and BMI. Higher rates of fibrosis (56.4% G1 vs. 29.2% G2 vs. 28.6% G3 p<0.001) and nonalcoholic steatohepatitis (NASH) (59.4% G1vs 49.2% G2 vs. 36% G3 p <0.001) were observed in the diabetic patients. Only 1.5 % of diabetics showed normal histology (vs. 7.76% G2 and 15.7% G3).

Introdução: A Doença Hepática Gordurosa Não Alcoólica (DHGNA) tem como causa principal a obesidade. Atualmente não existe tratamento medicamentoso específico para DHGNA. A cirurgia bariátrica surge como uma alternativa de tratamento em pacientes morbidamente obesos. Objetivos: Analisar, através de biópsia hepática intra-operatória, o grau de comprometimento hepático em obesos submetidos à cirurgia bariátrica, correlacionando os achados histopatológicos com o estado glicêmico dos pacientes. Métodos: Estudo de coorte prospectivo incluindo 521 pacientes submetidos à cirurgia bariátrica de julho de 2001 até dezembro de 2016. Os pacientes foram classificados em três grupos de acordo com o status glicêmico basal: 167(32,05%) diabéticos tipo 2 (G1), 132 (25,33%) pré-diabéticos (G2) e 222 (42,61%) obesos normoglicêmicos (G3). Foram obtidas biópsias hepáticas transoperatórias, as quais foram classificadas conforme os critérios de Brunt e do NASH-CRN. As variáveis clínicas e bioquímicas e histológicas foram comparadas antes da cirurgia e durante o seguimento pós-operatório. Resultados: A prevalência de DHGNA nesta coorte foi de 95%. Não houve diferença quanto ao gênero e IMC entre os grupos. Observaram-se taxas mais altas de fibrose (56,4% G1 vs 29,2% G2 vs 28,6% G3 p<0,001) e Esteatohepatite Não Alcoólica (EHNA) (59,4% G1vs 49,2% G2 vs 36% G3 p <0,001) nos pacientes diabéticos. Apenas 1,5 %, dos diabéticos apresentaram histologia normal (vs 7,76% G2 vs 15,7% G3). / Introduction: Obesity is the main cause of nonalcoholic fatty liver disease (NAFLD), for which there is currently no specific medical treatment. Bariatric surgery is a treatment alternative for morbidly obese patients. Objectives: Use an intraoperative liver biopsy to analyze the degree of liver damage in obese patients submitted to bariatric surgery and correlates the histopathological findings with glucose status. Methods: Prospective cohort study of 521 morbid obese patients undergoing bariatric surgery from July 2001 to December 2016, classified into three groups according to their baseline glucose status: 167 (32.05%) type 2 diabetes (G1), 132 (25.33%) pre-diabetic (G2) and 222 (42.61%) normoglycemic obese (G3). Patients using potentially hepatotoxic medications and a history of ethanol consumption or viral hepatitis were excluded. Intraoperative liver biopsies were obtained and classified in accordance with Brunt and NASH-CRN criteria. Clinical, biochemical and histopathological variables were compared before surgery and during postoperative follow-up. Results: The prevalence NAFLD was 95%. There was no intergroup difference for sex and BMI. Higher rates of fibrosis (56.4% G1 vs. 29.2% G2 vs. 28.6% G3 p<0.001) and nonalcoholic steatohepatitis (NASH) (59.4% G1vs 49.2% G2 vs. 36% G3 p <0.001) were observed in the diabetic patients. Only 1.5 % of diabetics showed normal histology (vs. 7.76% G2 and 15.7% G3).

Introdução: A Doença Hepática Gordurosa Não Alcoólica (DHGNA) tem como causa principal a obesidade. Atualmente não existe tratamento medicamentoso específico para DHGNA. A cirurgia bariátrica surge como uma alternativa de tratamento em pacientes morbidamente obesos. Objetivos: Analisar, através de biópsia hepática intra-operatória, o grau de comprometimento hepático em obesos submetidos à cirurgia bariátrica, correlacionando os achados histopatológicos com o estado glicêmico dos pacientes. Métodos: Estudo de coorte prospectivo incluindo 521 pacientes submetidos à cirurgia bariátrica de julho de 2001 até dezembro de 2016. Os pacientes foram classificados em três grupos de acordo com o status glicêmico basal: 167(32,05%) diabéticos tipo 2 (G1), 132 (25,33%) pré-diabéticos (G2) e 222 (42,61%) obesos normoglicêmicos (G3). Foram obtidas biópsias hepáticas transoperatórias, as quais foram classificadas conforme os critérios de Brunt e do NASH-CRN. As variáveis clínicas e bioquímicas e histológicas foram comparadas antes da cirurgia e durante o seguimento pós-operatório. Resultados: A prevalência de DHGNA nesta coorte foi de 95%. Não houve diferença quanto ao gênero e IMC entre os grupos. Observaram-se taxas mais altas de fibrose (56,4% G1 vs 29,2% G2 vs 28,6% G3 p<0,001) e Esteatohepatite Não Alcoólica (EHNA) (59,4% G1vs 49,2% G2 vs 36% G3 p <0,001) nos pacientes diabéticos. Apenas 1,5 %, dos diabéticos apresentaram histologia normal (vs 7,76% G2 vs 15,7% G3). / Introduction: Obesity is the main cause of nonalcoholic fatty liver disease (NAFLD), for which there is currently no specific medical treatment. Bariatric surgery is a treatment alternative for morbidly obese patients. Objectives: Use an intraoperative liver biopsy to analyze the degree of liver damage in obese patients submitted to bariatric surgery and correlates the histopathological findings with glucose status. Methods: Prospective cohort study of 521 morbid obese patients undergoing bariatric surgery from July 2001 to December 2016, classified into three groups according to their baseline glucose status: 167 (32.05%) type 2 diabetes (G1), 132 (25.33%) pre-diabetic (G2) and 222 (42.61%) normoglycemic obese (G3). Patients using potentially hepatotoxic medications and a history of ethanol consumption or viral hepatitis were excluded. Intraoperative liver biopsies were obtained and classified in accordance with Brunt and NASH-CRN criteria. Clinical, biochemical and histopathological variables were compared before surgery and during postoperative follow-up. Results: The prevalence NAFLD was 95%. There was no intergroup difference for sex and BMI. Higher rates of fibrosis (56.4% G1 vs. 29.2% G2 vs. 28.6% G3 p<0.001) and nonalcoholic steatohepatitis (NASH) (59.4% G1vs 49.2% G2 vs. 36% G3 p <0.001) were observed in the diabetic patients. Only 1.5 % of diabetics showed normal histology (vs. 7.76% G2 and 15.7% G3).

Contexte : La rémission du diabète de type 2 (DT2) à la suite d'une chirurgie bariatrique ou d'une restriction calorique sévère a été démontrée possible. Cependant, la faisabilité d’un programme d’interventions comportementales ne comprenant pas l’une de ces deux approches thérapeutiques, ainsi que son impact sur le taux de rémission du DT2 et la santé cardiovasculaire (CV), demeure à explorer. Aussi, les programmes de rémission du DT2 ont rarement été évalués dans le contexte d’un centre terciaire de cardiologie préventive et de réadaptation cardiaque. Méthodes : L'étude pilote DIABÉPIC 2 a évalué la faisabilité d'un programme de rémission du DT2 de 6 mois, basé sur une rééducation nutritionnelle (réduction des aliments ultra-transformés et adoption d'un régime méditerranéen modéré en glucides) et un entraînement aérobique et en résistance (3 x 60 min/semaine). De plus, une portion des participants (randomisation 2 :1) a ajouté le jeûne intermittent (JI) au cours des trois derniers mois. L’étude s’est déroulée au centre de cardiologie préventive et de réadaptation cardiaque de l’Institut de cardiologie de Montréal. Il avait été établi approprié de procéder à une étude clinique plus importante si le taux de recrutement atteignait 6 participants/mois et si un minimum de 70% des participants complétait le programme de 6 mois, avec un minimum de 70% de participation aux visites cliniques et de recherche. L'étude a aussi exploré l’impact des interventions sur le taux de rémission du DT2 et sur la santé cardiométabolique, les paramètres anthropométriques, la capacité cardiorespiratoire, la qualité de la matrice alimentaire et les performances neurocognitives. Résultats : La faisabilité a été démontrée avec un taux de recrutement de 6,4 participants/mois, 34 participants sur 42 (81 %) ayant complété le programme (41,2 % de femmes, âge moyen de 63,6 ± 9,2 ans, durée du DT2 de 7,4 ± 6,7 ans, Hb1Ac 6,7 ± 0,7 %) et une participation moyenne aux visites cliniques et de recherche de 87 %. Treize de ces 34 participants ont obtenu une rémission du DT2 (38 %), avec une perte de poids moyenne de 6,8 kg (-9,3 à -4,4, p <0,001). Les analyses exploratoires ont montré une amélioration significative des paramètres cardiométaboliques et anthropométriques, de la capacité cardiorespiratoire et de la qualité de la matrice alimentaire. Les participants randomisés pour l'intervention additionnelle de JI n’ont pas obtenu d’améliorations significativement différentes comparé au groupe contrôle. Conclusion : Les personnes atteintes de DT2 recevant des soins dans un centre tertiaire de cardiologie ont montré un intérêt et une capacité à s’engager dans un programme de rémission du DT2. Les interventions comportementales ont permis à 38% des participants d’atteindre les critères de rémission du DT2. Des études randomisées plus larges sont nécessaires pour confirmer l'efficacité d’un programme basé sur la rééducation nutritionnelle, l’entraînement physique et le JI. / Background: Remission of type 2 diabetes (T2D) following bariatric surgery or severe caloric restriction has been shown to be possible. However, the feasibility of a behavioral intervention program not including one of these two therapeutic approaches, as well as its impact on the remission rate of T2D and cardiovascular (CV) health, remains to be explored. Also, T2D remission programs have rarely been evaluated in the context of a tertiary preventive cardiology and cardiac rehabilitation center. Methods: The DIABÉPIC 2 pilot study evaluated the feasibility of a 6-month T2D remission program, based on nutritional re-education (reduction of ultra-processed foods and adoption of a Mediterranean diet moderate in carbohydrates) and training aerobic and resistance training (3 x 60 min/week). Additionally, a portion of participants (2:1 randomization) added intermittent fasting (IF) in the last three months. The study took place at the preventive cardiology and cardiac rehabilitation center of the Montreal Heart Institute. It was deemed appropriate to proceed with a larger clinical study if the recruitment rate reached 6 participants/month and if a minimum of 70% of participants completed the 6-month program, with a minimum of 70% participation in clinical and research visits. The study also explored the impact of interventions on T2D remission rate and on cardiometabolic and anthropometric parameters, cardiorespiratory fitness, quality of food matrix and neurocognitive performance. Results: Feasibility was demonstrated with a recruitment rate of 6.4 participants/month, 34 of 42 participants (81%) who completed the program (41.2% women, mean age of 63.6 ± 9.2 years, duration of T2D 7.4 ± 6.7 years, HbA1c 6.7 ± 0.7%) and with 87% attendance at assessment and intervention sessions. Thirteen of these 34 participants achieved remission of T2D (38 %), with a mean weight loss of 6.8 kg (-9.3 to -4.4, p < 0.001). Exploratory analyzes showed a significant improvement in cardiometabolic and anthropometric parameters, cardiorespiratory capacity and quality of the food matrix. Participants randomized to the additional IF intervention did not achieve significantly different improvements compared to the control group. Conclusion: People living with T2D and receiving care in a terciary cardiology center showed interest and ability to engage in a T2D remission program. Behavioral interventions enabled 38% of participants to achieve T2D remission criteria. Larger randomized studies are needed to confirm the effectiveness of a program based on nutritional re-education, physical training and IF.