Long-term Type 2 Diabetes Research Articles

Metformin-induced changes in the gut microbiome and plasma metabolome are associated with cognition in men

BackgroundAn altered gut microbiome characterized by reduced abundance of butyrate producing bacteria and reduced gene richness is associated with type 2 diabetes (T2D). An important complication of T2D is increased risk of cognitive impairment and dementia. The biguanide metformin is a commonly prescribed medication for the control of T2D and metformin treatment has been associated with a significant reduction in the risk of dementia and improved cognition, particularly in people with T2D. AimTo investigate the associations of metformin use with cognition exploring potential mechanisms by analyzing the gut microbiome and plasma metabolome using shotgun metagenomics and HPLC-ESI-MS/MS, respectively. MethodsWe explored two independent cohorts: an observational study (Aging Imageomics) and a phase IV, randomized, double-blind, parallel-group, randomized pilot study (MEIFLO). From the two studies, we analyzed four study groups: (1) individuals with no documented medical history or medical treatment (n = 172); (2) people with long-term T2D on metformin monotherapy (n = 134); (3) people with long-term T2D treated with oral hypoglycemic agents other than metformin (n = 45); (4) a newly diagnosed T2D subjects on metformin monotherapy (n = 22). Analyses were also performed stratifying by sex. ResultsSeveral bacterial species belonging to the Proteobacteria (Escherichia coli) and Verrucomicrobia (Akkermansia muciniphila) phyla were positively associated with metformin treatment, while bacterial species belonging to the Firmicutes phylum (Romboutsia timonensis, Romboutsia ilealis) were negatively associated. Due to the consistent increase in A. muciniphila and decrease in R.ilealis in people with T2D subjects treated with metformin, we investigated the association between this ratio and cognition. In the entire cohort of metformin-treated T2D subjects, the A.muciniphila/R.ilealis ratio was not significantly associated with cognitive test scores. However, after stratifying by sex, the A.muciniphila/R. ilealis ratio was significantly and positively associated with higher memory scores and improved memory in men.Metformin treatment was associated with an enrichment of microbial pathways involved in the TCA cycle, and butanoate, arginine, and proline metabolism in both cohorts. The bacterial genes involved in arginine metabolism, especially in production of glutamate (astA, astB, astC, astD, astE, putA), were enriched following metformin intake. In agreement, in the metabolomics analysis, metformin treatment was strongly associated with the amino acid proline, a metabolite involved in the metabolism of glutamate. ConclusionsThe beneficial effects of metformin may be mediated by changes in the composition of the gut microbiota and microbial-host-derived co-metabolites.

Validation of the Individualized Metabolic Surgery score in predicting long-term remission of diabetes after duodenal switch-type procedures.

To validate the Individualized Metabolic Surgery (IMS) score and assess long-term remission of type 2 diabetes (T2D) after duodenal switch (DS)-type procedures in patients with obesity. In addition, to help guide metabolic procedure selection for those patients categorized as having severe T2D. This is a retrospective single cohort study of all patients with T2D and severe obesity, who underwent DS-type procedures at a single institution from December 2010 to December 2018. Study endpoints included validating the IMS score in our cohort and evaluating the impact of DS-type procedures on long-term (≥ 5 years) remission of T2D, especially in patients with severe disease. A receiver operator characteristic curve was used to assess the accuracy of the IMS score using the area under the curve (AUC). The study cohort included 30 patients with complete baseline and long-term glycaemic data after their index DS-type surgery. Twelve patients (40%) were classified with severe T2D, and the distribution of IMS-based severity groups was similar between our cohort and the original IMS study (P = .42). IMS scores predicted long-term T2D remission with AUC = 0.77. Patients with IMS-based severe diabetes achieved significantly higher long-term remission after DS-type procedures compared with gastric bypass and/or sleeve gastrectomy from the original IMS study (42% vs. 12%; P < .05). The IMS score properly classifies the severity of T2D in our study cohort and adequately predicts its long-term remission after DS-type procedures. While T2D remission decreases with more severe IMS scores, long-term remission remains high after DS-type procedures among patients with severe disease.

Strategies to prevent Type 2 Diabetes in the postnatal period in women with history of Gestational Diabetes

This literature review emphasizes the critical need for focused interventions to prevent Type 2 Diabetes (T2D) in the postnatal period, particularly for women with a history of Gestational Diabetes Mellitus (GDM). GDM poses a substantial risk, increasing the likelihood of T2D development by 11-fold later in life. With 14% of pregnancies worldwide affected by GDM, the escalating global T2D rates underscore the urgency for targeted postnatal strategies. Current interventions, such as those modelled after the Diabetes Prevention Program (DPP) and the Mediterranean Diet, show promise in reducing T2D risk by over 50%, yet challenges like low engagement persist. To address these complexities, future research should prioritize developing acceptable postnatal interventions, incorporating peer support, addressing barriers, and employing randomized controlled trials with larger participant cohorts. The multidimensional approach involves lifestyle modifications, dietary changes, behaviour change strategies, and exploration of pharmacological options, collectively contributing to a substantial reduction in the long-term T2D risk for women with a history of GDM.

Postprandial Triglyceride, Glucose and Insulin Levels 10 Years After Bariatric Surgery in Women With Severe Obesity - A Pilot Study: Part 2 - Biliopancreatic Diversion.

Obesity significantly increases the risk of developing metabolic and cardiovascular diseases. The most effective management tool for both obesity and type 2 diabetes (T2D) is bariatric/metabolic surgery. Delayed postprandial plasma triglyceride clearance contributes to the development of atherosclerosis in patients with T2D. Biliopancreatic diversion (BPD) was shown to be the most effective procedure in long-term T2D remission. However, the effect of BPD on postprandial metabolic profile has not been studied so far. In this pilot study, we therefore examined the changes in postprandial glucose, insulin, and triglyceride in women with severe obesity and T2D before surgery and then two and ten years after BPD. The studied cohort included 7 women (mean age at baseline=49.3±8.2 years) with severe obesity (mean BMI= 45.7±2.9 kg/m?) and T2D. A standardized liquid mixed-meal test was carried out in all subjects and the mean postprandial levels of plasma glucose, insulin, and triglyceride were analyzed by standard laboratory procedures. For statistical evaluation, ANOVA with Bonferroni multiple comparisons was used. Ten years after BPD not only a significant reduction of an average BMI (F=32.9, p<0.001) but also significant declines in mean postprandial plasma levels of glucose (F=155.3, p<0.001), insulin (F=69.8, p<0.001), and triglyceride (F=139.9, p<0.001) were demonstrated. The observed changes in postprandial metabolic profile may contribute to improved cardiometabolic health after bariatric surgery.

Association of phenotypic frailty and frailty index with type 2 diabetes and dyslipidemia in middle-aged and elderly Chinese: A longitudinal cohort study

PurposeFrailty, type 2 diabetes (T2D) and dyslipidemia are highly prevalent in middle-aged and elderly populations. However, evidence on the longitudinal association of frailty with T2D and dyslipidemia is limited. The aim of our study was to explore the cross-sectional and longitudinal effects of frailty levels on T2D and dyslipidemia in combination with phenotypic frailty and frailty index (FI). Materials and methodsMultivariate logistic regression model was used to explore the association of frailty status with T2D and dyslipidemia. Area under curve (AUC) of the receiver operating characteristic curve (ROC) to estimate the predictive values of phenotypic frailty and frailty index for T2D and dyslipidemia. In addition, depressive symptom was used as a mediating variable to examine whether it mediates the association between frailty and T2D or dyslipidemia. Results10,203 and 9587 participants were chosen for the longitudinal association analysis of frailty with T2D and dyslipidemia. Frailty was associated with T2D (phenotypic frailty: OR=1.50, 95 %CI=1.03, 2.17; FI: OR=1.17, 95 %CI=1.08, 1.26) and dyslipidemia (phenotypic frailty: OR=1.56, 95 %CI=1.16, 2.10; FI: OR=1.17, 95 %CI=1.10, 1.25). Phenotypic frailty and frailty index significantly improved the risk discrimination of T2D and dyslipidemia (p<0.05). Depressive symptoms played a mediating role in the association between frailty and long-term T2D or dyslipidemia (p<0.05). ConclusionFrailty had adverse effects on type 2 diabetes and dyslipidemia, with depressive symptoms acting as the mediator.

The Impact of the COVID-19 Pandemic in The Netherlands on Primary Healthcare Use and Clinical Outcomes in Persons with Type 2 Diabetes

The COVID-19 pandemic has had a significant impact on healthcare systems worldwide, including the postponing or canceling of appointments and procedures for type 2 diabetes (T2D) care by general practitioners (GPs) in the Netherlands. The aim of this study was to investigate the impact of the COVID-19 pandemic on primary healthcare use and clinical measurements for people with T2D. Additionally, we aimed to determine if changes were observed among specific risk groups: (1) persons 70 years or older, or below 70 years, (2) patients who were meeting their HbA1c targets and those who were not, and (3) patients with high-risk and non-high-risk T2D. This retrospective cohort study among persons with T2D was conducted using data from the DIAbetes MANagement and Treatment (DIAMANT) data infrastructure, deriving data from electronic medical records of Dutch GPs. The study assessed GP visit counts, and counts and values of clinical measurements, including hemoglobin A1c (HbA1c), body mass index (BMI), low-density lipoprotein (LDL) cholesterol, and systolic blood pressure (SBP). Adjusted negative binomial (NB) regression and generalized estimating equations (GEE) models were used to estimate GP visit counts and population averages of clinical measurements, respectively, comparing 2019 (pre-pandemic) with 2020 (during the pandemic). Changes in specific groups were examined by stratifying outcomes for the aforementioned subgroups. The cohort consisted of 182,048 patients with T2D (47% female, mean age 69 ± 13 years) on 1 March 2019, of which 168,097 persons (92%) still contributed follow-up data in 2020. We observed an increase in total GP visits in 2020, with an adjusted rate ratio (RR) of 1.09 (95% CI 1.08–1.09). The frequency increased for office visits (RR 1.06; 1.06–1.07) and phone calls (RR 1.33; 1.31–1.35) but remained stable for home visits (RR 1.02; 0.99–1.04). On both population and individual levels, HbA1c values increased in 2020 by 1.65 (1.59–1.70) mmol/mol compared to 2019. Observed changes in 2020 for BMI, LDL, and SBP values were also statistically significant but small. Subgroup stratifications showed higher scores of all clinical measurements in younger persons (&lt;70 years), those who met their HbA1c target, and non-high-risk T2D patients than their respective high-risk subgroups. During the first year of the COVID-19 pandemic in the Netherlands, changes in primary healthcare use were observed among persons with T2D, with an increase in GP office visits and phone calls and a decreased number of clinical measurements and GP home visits. HbA1c levels increased among patients with T2D in 2020. Further research is necessary to determine the impact of the COVID-19 pandemic on long-term clinical outcomes and (long-term) T2D complications.

Comparison of various prediction models in the effect of Roux-en-Y gastric bypass on type 2 diabetes in the Chinese population 5 years after surgery.

Various prediction models of type 2 diabetes (T2D) remission have been externally verified internationally. However, long-term validated results after Roux-en-Y gastric bypass (RYGB) surgery are lacking. The best model for the Chinese population is also unknown. To evaluate the prediction effect of various prediction models on the long-term diabetes remission after RYGB in the Chinese population and to provide reference for clinical use. A retrospective clinical study at a university hospital. We retrospectively analyzed Chinese population data 5 years after RYGB and externally validated 11 predictive models to evaluate the predictive effect of each model on long-term T2D remission after RYGB. We enrolled 84 patients. The mean body mass index was 41 kg/m2, and the percentage of excess weight loss (%EWL) was 72.3%. The mean glycated hemoglobin level was 8.4% preoperatively and decreased to 5.9% after 5 years. The 5-year postoperative complete and partial remission rates of T2D were 31% and 70.2%, respectively. The ABCD scoring model (sensitivity, 84%; specificity, 76%; area under the curve [AUC], .866) and the Panuzi etal. [34] study (sensitivity, 84%; specificity, 81%; AUC, .842) showed excellent results. In the Hosmer-Lemeshow goodness-of-fit test, calibration values for ABCD and Panuzi etal. [34] were .14 and .21, respectively. The predicted-to-observed ratios of ABCD and Panuzi etal. [34] were .83 and .88, respectively. T2D was relieved to varying degrees 5 years after RYGB in patients with obesity. Theprediction models in ABCD and the Panuzi etal. [34] studies showed the best prediction effects. ABCD was recommended for clinical use because of excellent predictive performance, goodstatistical test results, and simple and practical design features.

Weight-loss Independent Clinical and Metabolic Biomarkers Associated with Type 2 Diabetes Remission Post-bariatric/metabolic Surgery

PurposeRemission of type 2 diabetes (T2D) can be achieved by many, but not all, people following bariatric/metabolic surgery. The mechanisms underlying T2D remission remain incompletely understood. This observational study aimed to identify novel weight-loss independent clinical, metabolic and genetic factors that associate with T2D remission using comprehensive phenotyping.Materials and MethodsTen patients without T2D remission (non-remitters) were matched to 10 patients with T2D remission (remitters) for age, sex, type of surgery, body weight, BMI, post-operative weight loss, duration from surgery and duration of T2D. Detailed body composition assessed using magnetic resonance imaging, gut hormones, serum metabolomics, insulin sensitivity, and genetic risk scores for T2D and anthropometric traits were assessed.ResultsRemitters had significantly greater β-cell function and circulating acyl ghrelin levels, but lower visceral adipose tissue (VAT): subcutaneous adipose tissue (SAT) ratio than non-remitters. Branched-chain amino acids (BCAAs) and VLDL particle size were the most discriminant metabolites between groups. A significant positive correlation between, VAT area, VAT:SAT ratio and circulating levels of BCAAs was observed, whereas a significant negative correlation between BCAAs and β-cell function was revealed.ConclusionWe highlight a potentially novel relationship between VAT and BCAAs, which may play a role in glucoregulatory control. Improvement in β-cell function, and the role ghrelin plays in its recovery, is likely another key factor influencing T2D remission post-surgery. These findings suggest that adjunctive approaches that target VAT loss and restoration of BCAA metabolism might achieve higher rates of long-term T2D remission post-surgery.Graphical

Long-term remission of type 2 diabetes through intense lifestyle modification program - A case series.

Type 2 diabetes (T2D) remission is being widely accepted and documented as feasible through calorie restriction and bariatric surgery. Recent studies with lifestyle changes have also shown T2D remission; however, long-term remission through lifestyle modifications is not yet established. Though glycated hemoglobin (HbA1c) is a universally accepted indicator of glycemic status, oral glucose tolerance test (OGTT) would be a more robust marker in understanding whether the metabolic abnormalities in glucose metabolism have undergone complete remission as well. We present a case series of four patients enrolled in the Holistic Transformation Program, a lifestyle modification program, between 2016 and 2018. The intervention was a combination of a vegan diet, structured exercises, and stress management delivered over 12 months. All four patients successfully achieved T2D remission and cleared OGTT consecutively for a minimum period of 3 years. Our findings suggest that long-term T2D remission may be possible through lifestyle modification.

Longitudinal alterations in bone morphometry, mechanical integrity and composition in Type-2 diabetes in a Zucker diabetic fatty (ZDF) rat.

Individuals with Type-2 Diabetes (T2D) have an increased risk of bone fracture, without a reduction in bone mineral density. It is hypothesised that the hyperglycaemic state caused by T2D forms an excess of Advanced Glycated End-products (AGEs) in the organic matrix of bone, which are thought to stiffen the collagen network and lead to impaired mechanical properties. However, the mechanisms are not well understood. This study aimed to investigate the geometrical, structural and material properties of diabetic cortical bone during the development and progression of T2D in ZDF (fa/fa) rats at 12-, 26- and 46-weeks of age. Longitudinal bone growth was impaired as early as 12-weeks of age and by 46-weeks bone size was significantly reduced in ZDF (fa/fa) rats versus controls (fa/+). Diabetic rats had significant structural deficits, such as bending rigidity, ultimate moment and energy-to-failure measured via three-point bend testing. Tissue material properties, measured by taking bone geometry into account, were altered as the disease progressed, with significant reductions in yield and ultimate strength for ZDF (fa/fa) rats at 46-weeks. FTIR analysis on cortical bone powder demonstrated that the tissue material deficits coincided with changes in tissue composition, in ZDF (fa/fa) rats with long-term diabetes having a reduced carbonate:phosphate ratio and increased acid phosphate content when compared to age-matched controls, indicative of an altered bone turnover process. AGE accumulation, measured via fluorescent assays, was higher in the skin of ZDF (fa/fa) rats with long-term T2D, bone AGEs did not differ between strains and neither AGEs correlated with bone strength. In conclusion, bone fragility in the diabetic ZDF (fa/fa) rats likely occurs through a multifactorial mechanism influenced initially by impaired bone growth and development and proceeding to an altered bone turnover process that reduces bone quality and impairs biomechanical properties as the disease progresses.

Validation of the individualized metabolic surgery score for bariatric procedure selection in the merged data of two randomized clinical trials (SLEEVEPASS and SM-BOSS).

LSG and LRYGB are globally the most common bariatric procedures. IMS score categorizes T2D severity (mild, moderate, and severe) based on 4 independent preoperative predictors of long-term remission as follows: T2D duration, number of diabetes medications, insulin use, and glycemic control. IMS score has not been validated in a randomized patient cohort. To assess the feasibility of individualized metabolic surgery (IMS) score in facilitating procedure selection between laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) for patients with severe obesity and type 2 diabetes (T2D). Merged individual patient-level 5-year data of 2 large randomized clinical trials (SLEEVEPASS and SM-BOSS [Swiss Multicenter Bypass or Sleeve Study]). IMS score was calculated for study patients and its performance was analyzed. One hundred thirty-nine out of 155 patients with T2D had available preoperative data to calculate IMS score as follows: mild stage (n = 41/139), moderate stage (n = 77/139), severe stage (n = 21/139). At 5 years, 135 (87.1%, 67 LSG/68 LRYGB) were available for follow-up and 121 patients had both pre- and postoperative data. Diabetes remission rates according to preoperative IMS score were as follows: mild stage 87.5% (n = 14/16) after LSG and 85.7% (n = 18/21) after LRYGB (P = .999), moderate stage 42.9% (n = 15/35) and 45.2% (n = 14/31) (P = .999), and severe stage 18.2% (n = 2/11) and 0% (n = 0/7) (P = .497), respectively. The T2D remission rate varied significantly between the stages as follows: mild versus moderate odds ratio (OR) 8.3 (95% CI, 2.8-24.0; P < .001), mild versus severe OR 52.2 (95% CI 9.0-302.3; P < .001), and moderate versus severe OR 6.3 (95% CI, 1.3-29.8; P = .020). In our study, remission rates of T2D were not statistically different after LSG and LRYGB among all patients and among patients with mild, moderate, and severe diabetes stratified by the IMS score. However, the study may be underpowered to detect differences due to small number of patients in each subgroup. IMS score seemed to be useful in predicting long-term T2D remission after bariatric surgery.

Urinary Markers of Tubular Injury and Renal Fibrosis in Patients with Type 2 Diabetes and Different Phenotypes of Chronic Kidney Disease

This study assessed the urinary excretion of markers and mediators of tubular injury and renal fibrosis in patients with type 2 diabetes (T2D) and non-albuminuric and albuminuric patterns of chronic kidney disease (CKD). One hundred and forty patients with long-term T2D and different patterns of CKD and twenty non-diabetic individuals were included. Urinary retinol-binding protein 4 (RBP-4), glutathione-S-transferase α1 and π (GST-α1 and GST-π), transforming growth factor β (TGF-β), type I and type IV collagen (Col1 and Col4), bone morphogenic protein 7 (BMP-7), and hepatocyte growth factor (HGF) were assessed by ELISA. Patients with T2D demonstrated increased urinary excretion of RBP-4, GST-π, Col4, BMP-7, and HGF (all p < 0.05 vs. control). The excretion of RBP-4, GST-π, Col1, and Col4 was increased in patients with elevated albumin-to-creatinine ratio (UACR; all p < 0.05 vs. control), while BMP-7 and HGF were increased innormoalbuminuric patients also (p < 0.05). Urinary RBP-4, GST-α1, Col1, Col4, and HGF correlated positively with UACR; meanwhile, no correlations with glomerular filtration rate were found. The results demonstrate that elevated urinary excretions of the markers of tubular injury (RBP-4, GST-π) and renal fibrosis (Col1, Col4), as well as HGF, an antifibrotic regulator, are associated with the albuminuric pattern of CKD in subjects with T2D.

Diabetic microenvironment preconditioning of adipose tissue-derived mesenchymal stem cells enhances their anti-diabetic, anti-long-term complications, and anti-inflammatory effects in type 2 diabetic rats

BackgroundMesenchymal stem cells (MSCs) exert anti-diabetic effects and improve long-term complications via secretory effects that regulate macrophage polarisation and attenuate inflammation. Enhancing the efficacy of MSCs needs to be explored further. The in vitro culture microenvironment influences the secretory profile of MSCs. Therefore, we hypothesised that a diabetic microenvironment would promote the secretion of cytokines responsible for macrophage polarisation, further attenuating systemic inflammation and enhancing the effects of MSCs on type 2 diabetes (T2D) and long-term diabetic complications.MethodsPreconditioned adipose-derived mesenchymal stem cells (pre-ADSCs) were obtained after co-cultivating ADSCs in a diabetic metabolic environment (including high sugar, advanced glycation end-product, and lipopolysaccharides). The regulatory effects of pre-ADSCs on macrophages were observed in vitro. A T2D rat model was induced with a high-fat diet for 32 weeks combined with an intraperitoneal injection of streptozotocin. Sprague–Dawley (SD) rats were divided into four groups: normal group, diabetes without treatment group (PBS), ADSC treatment group, and pre-ADSC treatment group. ADSCs and pre-ADSCs were intravenously administered weekly to SD rats for 6 months, and then glucose homeostasis and long-term diabetic complications were evaluated in each group.ResultsThe secretion of cytokines related to M2 macrophage polarisation (IL-6, MCP-1, etc.) was increased in the pre-ADSC group in the in vitro model. Pre-ADSC treatment significantly maintained blood glucose homeostasis, reduced insulin resistance, promoted islet regeneration, and ameliorated the complications related to diabetes in rats (chronic kidney disease, non-alcoholic steatohepatitis, lung fibrosis, and cataract) compared to the ADSC group (P < 0.05). Additionally, the number of anti-inflammatory M2 macrophage phenotypes was enhanced in tissues following pre-ADSC injections. Moreover, the expression of pro-inflammatory genes (iNOS, TNF-α, IL-1β) was reduced whereas that of anti-inflammatory genes (Arg1, CD206, and Il-10) was increased after cultivation with pre-ADSCs.ConclusionDiabetic microenvironment-preconditioned ADSCs effectively strengthen the capacity against inflammation and modulate the progress of long-term T2D complications.

1421-P: Long-Term Type 2 Diabetes Remission after Bariatric Surgery in Patients with and without Liver Steatosis

Background: Nonalcoholic steatohepatitis (NASH) is considered the hepatic manifestation of insulin resistance. Therefore, we aimed to assess the association between biopsy-proven liver steatosis and long-term remission of type 2 diabetes (T2D) 8 years following different bariatric procedures. Methods: In a retrospective cohort study including 249 patients with and without T2D, the association between biopsy-proven NASH and long-term remission of T2D 8 years following sleeve gastrectomy (SG) and Roux-enY-gastric bypass (RYGB) has been assessed. Results: Out of 249 patients, 15.3% showed NASH and T2D at the time of surgery. 8 years after surgery, T2D remission was achieved in 44.7% of patients with NASH compared to 76.0% without NASH. Patients with T2D remission were younger, had higher BMI, displayed lower HbA1c and lower preoperative insulin use (p&amp;lt;0.001) . Patients without remission of T2D showed higher steatosis scores (p&amp;lt;0.05) . In a multivariate logistic regression, higher preoperative HbA1c (OR 0.41) , insulin use (OR 0.16) and preexisting liver fibrosis (OR 0.19) decreased the probability of long-term T2D remission (p&amp;lt;0.05) . Liver steatosis, hepatocyte ballooning or lobular inflammation were not significantly associated with T2D remission. Patients without T2D were predominantly female, of younger age (p&amp;lt;0.001) and displayed lower scores of steatosis, hepatocyte ballooning and lobular inflammation (p&amp;lt;0.05) . With regard to type of surgery, there was no significant difference in T2D remission. Discussion and Conclusion: Our data suggest that long-term remission of T2D after bariatric surgery (BS) is associated with lower preoperative insulin use and lower biopsy-proven steatosis scores in patients with NASH. Furthermore, T2D remission might be less likely in patients with liver fibrosis. Type of surgery did not affect T2D remission. Our results might help identify patients with NAFLD who benefit most from BS with regard to glycemic outcomes long-term. Disclosure A.Lautenbach: Advisory Panel; Novo Nordisk, Speaker's Bureau; Boehringer Ingelheim International GmbH, Novo Nordisk. M.Wernecke: None. S.M.Meyhöfer: None. S.Meyhöfer: None. F.D.Stoll: None. J.Aberel: Advisory Panel; Novo Nordisk, Speaker's Bureau; Novo Nordisk.

IDF21-0401 How accurate are DiaRem, Ad-DiaRem or DiaBetter scores in predicting diabetes remission 10 years after gastric bypass?

Background: The vast majority of patients submitted to Roux-en-Y Gastric Bypass (RYGB) experience substantial and sustained weight loss, as well as significant improvement or resolution of obesity-associated comorbidities, and most particularly Type 2 Diabetes (T2D). However, up to 20% of operated patients fail to benefit from surgery in terms of weight loss or diabetes control. A percentage that tends to increase along the post-operative timespan. The accuracy of DiaRem, Ad-DiaRem and DiaBetter scores, based on pre-operative parameters, for predicting short-term T2D remission after bariatric surgery was previously demonstrated. None of these scores were yet assessed for the possibility of predicting long-term T2D remission. Aim: This study aim was to evaluate DiaRem, Ad-DiaRem and DiaBetter accuracy at predicting T2D remission more than 10 years after RYGB surgery. Method: Patients with obesity and T2D (n=72) submitted to RYGB for the primary treatment of obesity with 10 or more years of follow-up were included in this study. All patients had surgery performed by the same team at a single hospital center. From those patients pre-operative anthropometric and clinical data was retrieved to calculate DiaRem, Ad-DiaRem and DiaBetter scores and a clinical evaluation was conducted to assess diabetes status. Scores accuracy in predicting long-term T2D remission was estimated by calculating the receiver operating characteristic (ROC) area under the curve (AUC). Results: From all patients with pre-operative T2D (n=72), 39 subjects (53.4%) achieved and maintained T2D remission 10 or more years after RYGB. The DiaRem score (AUC=0.826) depicted the highest discriminative power to predict long-term T2D remission than Ad-DiaRem (AUC=0.760) and DiaBetter (AUC=0.778). Pre-operative T2D diagnosis duration does not seem to be a good predictor of long-term T2D remission, in contrast to what is reported for short-term T2D remission prediction. Discussion: Our study demonstrated that DiaRem has a higher accuracy than Ad-DiaRem and DiaBetter scores to predict long-term T2D remission after RYGB surgery. Nevertheless, these scores accuracy to predict long-term T2D remission is lower than reported for short-term T2D remission prediction by previous studies. Thus, a better scoring system optimized for predicting long-term T2D after bariatric surgery is still needed.

Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health Study.

SummaryBackgroundMetabolomics profiles were consistently associated with type 2 diabetes (T2D) risk, but evidence on long-term metabolite changes and T2D incidence is lacking. We examined the associations of 10-year plasma metabolite changes with subsequent T2D risk.MethodsWe conducted a nested T2D case-control study (n=244 cases, n=244 matched controls) within the Nurses' Health Study. Repeated metabolomics profiling (170 targeted metabolites) was conducted in participant blood specimens from 1989/1990 and 2000/2001, and T2D occurred between 2002 and 2008. We related 10-year metabolite changes (Δ-values) to subsequent T2D risk using conditional logistic models, adjusting for baseline metabolite levels and baseline levels and concurrent changes of BMI, diet quality, physical activity, and smoking status.FindingsThe 10-year changes of thirty-one metabolites were associated with subsequent T2D risk (false discovery rate-adjusted p-values [FDR]<0.05). The top three high T2D risk-associated 10-year changes were (odds ratio [OR] per standard deviation [SD], 95%CI): Δisoleucine (2.72, 1.97-3.79), Δleucine (2.53, 1.86-3.47), and Δvaline (1.93, 1.52-2.44); other high-risk-associated metabolite changes included alanine, tri-/diacylglycerol-fragments, short-chain acylcarnitines, phosphatidylethanolamines, some vitamins, and bile acids (ORs per SD between 1.31and 1.82). The top three low T2D risk-associated 10-year metabolite changes were (OR per SD, 95% CI): ΔN-acetylaspartic acid (0.54, 0.42-0.70), ΔC20:0 lysophosphatidylethanolamine (0.68, 0.56-0.82), and ΔC16:1 sphingomyelin (0.68, 0.56-0.83); 10-year changes of other sphingomyelins, plasmalogens, glutamine, and glycine were also associated with lower subsequent T2D risk (ORs per SD between 0.66 and 0.78).InterpretationRepeated metabolomics profiles reflecting the long-term deterioration of amino acid and lipid metabolism are associated with subsequent risk of T2D.

Incorporating Post-Cessation Weight-Control Coaching into Smoking Cessation Therapy to Reduce Type 2 Diabetes Risk.

Post-cessation weight gain (PCWG) facilitates short-term type 2 diabetes (T2D) risk in prediabetic smokers in the absence of complementary measures. In this shared decision-making-based non-randomized controlled trial, prediabetic smokers joined the Fight Tobacco and Stay Fit (FIT2) program or received usual care. The 16-week FIT2 program combined smoking cessation therapy with individualized coaching in diet and physical activity strategies for PCWG restriction (NCT01926041 at ClinicalTrials.gov). During a mean follow-up period of 1316 days, 217 participants (36.8%) developed T2D, and 68 (11.5%) regressed to normoglycemia. In the intention-to-treat analysis (n = 589), the FIT2 program was associated with a reduced T2D risk (HR, 0.58; 95% CI, 0.40–0.84) and a higher probability of regression to normoglycemia (HR, 1.91; 95% CI, 1.04–3.53) compared with usual care. The post-program quitters were at lower T2D risk (HR, 0.63; 95% CI, 0.44–0.92) and were more likely to regress to normoglycemia (HR, 1.83; 95% CI, 1.01–3.30) compared with the controls in the time-varying analysis (n = 532). We demonstrated that the FIT2 program was negatively associated with long-term T2D risk and positively associated with the probability of regression to normoglycemia compared with usual care. To prevent T2D development, we recommend simultaneously promoting smoking abstinence and lifestyle coaching for PCWG restriction.

Distinct associations of self-monitoring of blood glucose with glycemic control and hypoglycemia between groups of recently diagnosed and long-term follow-up type 2 diabetes: The Taiwan Diabetes Registry.

We investigated the uses and frequency of self-monitoring of blood glucose (SMBG) with glycemic control and hypoglycemia in two groups of type 2 diabetes (T2D) (recently diagnosed and long-term follow-up) using real-world data in Taiwan (the Taiwan Diabetes Registry). Patients with T2D recently diagnosed within 6months (n=3297, mean age 54.4±13.9years) and T2D patients with long-term follow-up (n=1201, mean age 65.5±12.1years, mean diabetes duration 14.3±7.8years) from the Taiwan Diabetes Registry were analysed. All patients were interviewed by certified diabetes educators. Information about SMBG and hypoglycemia was recorded. Demography, personal history, and laboratory data were obtained from electronic medical records. Logistic regression analyses were used to examine the associations of SMBG with glycated haemoglobin (HbA1c) <7% and hypoglycemia. Mean HbA1c values were 8.4±2.5 and 7.6±1.4%, respectively, in the recently diagnosed and long-term follow-up T2D groups. The self-reported rates of hypoglycemic events within 3months were 10.5% and 19.0%, respectively. SMBG was associated with higher odds of HbA1c <7% (OR 1.21, 95% CI 1.01-1.44) in patients with recently diagnosed T2D, but with lower odds of HbA1c <7% in T2D patients with long-term follow-up (OR 0.60, 95% CI 0.44-0.82). In both study populations, SMBG was independently associated with hypoglycemia (OR 3.90 [95% CI 2.99-5.08] and OR 3.93 [95% CI 2.73-5.66], respectively). The aforementioned findings were consistent across the strata of SMBG frequency. We reported different associations between SMBG and glycemic control in patients recently diagnosed with T2D and in T2D patients with long-term follow-up. SMBG was associated with higher detection of hypoglycemic episodes in both study populations.

Association of Childhood Fat Mass and Weight With Adult-Onset Type 2 Diabetes in Denmark

Childhood obesity, defined by cutoffs based on the weight-based marker of body mass index, is associated with adult type 2 diabetes (T2D) risk. Whether childhood fat mass (FM) is the driver of these associations is currently unknown. To quantify and compare height-independent associations between childhood FM and weight with adult T2D risk in a historic Danish cohort. This population-based retrospective cohort study included schoolchildren from The Copenhagen School Health Records Register born between January 1930 and December 1985 with follow-up to adulthood through December 31, 2015. Analyses were based on 269 913 schoolchildren aged 10 years with 21 896 established adult T2D cases and 261 192 children aged 13 years with 21 530 established adult T2D cases for whom childhood height and weight measurements, as well as predicted FM, were available. Statistical analyses were performed between April 2019 to August 2020. Childhood FM and weight at ages 10 and 13 years. Diagnoses of T2D were established by linkage to national disease registers for adults aged at least 30 years. Sex-specific Cox regression quantified associations, adjusted for childhood height, which were evaluated within 5 birth-cohort groups. Group-specific results were pooled using random-effects meta-analyses accounting for heterogeneity across group-specific associations. This cohort study analyzed data from 269 913 children aged 10 years (135 940 boys [50.4%]) with 21 896 established adult T2D cases and 261 192 children aged 13 years (131 025 boys [50.2%]) with 21 530 established adult T2D cases. After adjusting for childhood height, increases in FM and weight (per kilogram) among boys aged 10 years were associated with elevated T2D risks at age 50 years of 12% (hazard ratio [HR], 1.12; 95% CI, 1.10-1.14) and 7% (HR, 1.07; 95% CI, 1.05-1.09), respectively, and among girls aged 10 years of 15% (HR, 1.15; 95% CI, 1.13-1.17) and 10% (HR, 1.10; 95% CI, 1.08-1.11), respectively. Among children aged 13 years, increases in FM and weight (per kilogram) were associated with increased T2D risks at age 50 years of 10% (HR, 1.10; 95% CI, 1.09-1.10) and 6% (HR, 1.06; 95% CI, 1.05-1.07) for boys, respectively, and of 10% (HR, 1.10; 95% CI, 1.10-1.11) and 7% (HR, 1.07; 95% CI, 1.06-1.08), respectively, for girls. This cohort study found that a 1-kg increase in childhood FM was more strongly associated with increased adult T2D risk than a 1-kg increase in weight, independent of childhood height. Information on FM, rather than weight-based measures, focuses on a modifiable component of weight that may be associated with adult T2D risk. These findings support the assessment of childhood FM in adiposity surveillance initiatives in an effort to reduce long-term T2D risk.

Predictive Model of Type 2 Diabetes Remission after Metabolic Surgery in Chinese Patients.

Introduction Metabolic surgery is an effective treatment for type 2 diabetes (T2D). At present, there is no authoritative standard for predicting postoperative T2D remission in clinical use. In general, East Asian patients with T2D have a lower body mass index and worse islet function than westerners. We aimed to look for clinical predictors of T2D remission after metabolic surgery in Chinese patients, which may provide insights for patient selection. Methods Patients with T2D who underwent metabolic surgery at the Third Xiangya Hospital between October 2008 and March 2017 were enrolled. T2D remission was defined as an HbA1c level below 6.5% and an FPG concentration below 7.1 mmol/L for at least one year in the absence of antidiabetic medications. Results (1) Independent predictors of short-term T2D remission (1-2 years) were age and C-peptide area under the curve (C-peptide AUC); independent predictors of long-term T2D remission (4–6 years) were C-peptide AUC and fasting plasma glucose (FPG). (2) The optimal cutoff value for C-peptide AUC in predicting T2D remission was 30.93 ng/ml, with a specificity of 67.3% and sensitivity of 75.8% in the short term and with a specificity of 61.9% and sensitivity of 81.5% in the long term, respectively. The areas under the ROC curves are 0.674 and 0.623 in the short term and long term, respectively. (3) We used three variables (age, C-peptide AUC, and FPG) to construct a remission prediction score (ACF), a multidimensional 9-point scale, along which greater scores indicate a better chance of T2D remission. We compared our scoring system with other reported models (ABCD, DiaRem, and IMS). The ACF scoring system had the best distribution of patients and prognostic significance according to the ROC curves. Conclusion Presurgery age, C-peptide AUC, and FPG are independent predictors of T2D remission after metabolic surgery. Among these, C-peptide AUC plays a decisive role in both short- and long-term remission prediction, and the optimal cutoff value for C-peptide AUC in predicting T2D remission was 30.93 ng/ml, with moderate predictive values. The ACF score is a simple reliable system that can predict T2D remission among Chinese patients.