INVESTIGATING THE CORRELATIONS BETWEEN SUBSTANCE P, ANTIOXIDANT LEVELS, AND METABOLIC MARKERS IN NON-OBESE TYPE 2 DIABETIC PATIENTS.

Hyperglycemia and hyperinsulinemia in type 2 diabetes result in complications exacerbated by oxidative stress, leading to cardiovascular, nephropathic, neuropathic, and retinopathic problems. Substance P(SP), a natural neuropeptide, inhibits cell death and enhances cell growth during oxidative or inflammatory stress, suggesting a potential role in reducing diabetic complications. Objective -investigate serum levels of SP, total antioxidant status (TAS), glycemic measures, and lipid profiles in non-obese type 2 diabetic patients and evaluate the relationships involving these biomarkers. MATERIAL AND METHOD: A case-control study involved 85 adult subjects (46males & 39females), aged (30-60) year, included two groups; diabetic group:53(males & females) non-obese type 2 diabetic patients, healthy group: Apparently healthy subjects of 32 individuals chosen from the general population and matched with patients age, sex and BMI. RESULTS: The results showed that patients' glucose levels increased as percentage increase of (˃141%),mild elevated insulin levels (˃50%), higher insulin resistance (˃250%), the lipid parameters exhibited disruption in comparison to the control group, in diabetic group, the serum levels of TAS, SP decreased considerably in comparison to the control group. CONCLUSION: As evidenced by the outcomes; the TAS showed significant negative correlations with fasting serum glucose and low-density lipoprotein, and positive correlations with high-density lipoprotein. Neither the glycemic indices nor the lipid profiles or TAS demonstrated any notable associations with SP levels. This suggests that while SP levels are reduced in type 2 diabetes, they do not appear to be directly linked with the measured biomarkers.

Association between the AHA life's essential 8 and prediabetes/diabetes: a cross-sectional NHANES study.

Background and aims: The American Heart Association (AHA) recently introduced the Life's Essential 8 (LE8) to improve cardiovascular health (CVH). However, the association between LE8 and the risk of prediabetes or diabetes is not yet fully understood. Consequently, this study aims to assess the association between CVH, as evaluated by LE8, and the risk of prediabetes and diabetes. Methods and Results: This cross-sectional study encompassed 7,739 participants aged ≥20 years from the 2007-2018 National Health and Nutrition Examination Surveys (NHANES). The CVH of participants was evaluated using the LE8, combining four health behaviors and three health factors. Glucose metabolic status categories included normal glucose metabolism, prediabetes including isolated impaired fasting glucose, isolated impaired glucose tolerance, both IFG and IGT, and diabetes. The associations between CVH and prediabetes and diabetes were analyzed using logistic regression, linear regression, restricted cubic splines, and subgroup analyses. Among 7,739 participants, 1,949 had iIFG, 1,165 were diagnosed with iIGT, 799 were IFG+IGT, and 537 were diagnosed with diabetes. After multivariable adjustments, CVH scores were inversely associated with prediabetes and diabetes, with the most robust inverse association observed between IFG+IGT and CVH across all prediabetes subgroups. Of all CVH components not directly in the causal pathway, body mass index (BMI) had the most robust associations with prediabetes and diabetes. Subgroup analyses indicated that the negative correlation between CVH and prediabetes was stronger among those with university or higher education. Conclusion: CVH, as defined by LE8, showed a significant negative association with prediabetes and diabetes.

Circulating glutamine/glutamate ratio is closely associated with type 2 diabetes and its associated complications.

Objective: This study aims to conduct a comprehensive investigation of the serum amino acid profiles of individuals with type 2 diabetes (T2D) and its related complications. Methods: Patients with T2D were enrolled in this study. Sixteen kinds of common amino acids in the fasting circulating were assessed through liquid chromatography-mass spectrometry (LC-MS). Subsequently, correlation, regression analyses, and receiver operating characteristic (ROC) curves were conducted to assess the associations between amino acids and clinical indicators. Results: Thirteen different kinds of amino acids were identified in diabetic patients, as compared with normal controls. The Glutamine/Glutamate (Gln/Glu) ratio was negatively correlated with BMI, HbA1c, serum uric acid, and the triglyceride-glucose (TyG) index, while it was positively correlated with HDL-C. Logistic regression analyses indicated that Gln/Glu was a consistent protective factor for both T2D (OR = 0.65, 95% CI 0.50-0.86) and obesity (OR = 0.79, 95% CI 0.66-0.96). The ROC curves demonstrated that Gln/Glu, proline, valine, and leucine provided effective predictions for diabetes risk, with Gln/Glu exhibiting the highest AUC [0.767 (0.678-0.856)]. In patients with T2D, Gln was the only amino acid that displayed a negative correlation with HbA1c (r = -0.228, p = 0.017). Furthermore, HOMA-ß exhibited a negative correlation with Glu (r = -0.301, p = 0.003) but a positive correlation with Gln/Glu (r = 0.245, p = 0.017). Notably, logistic regression analyses revealed an inverse correlation of Gln/Glu with the risk of diabetic kidney disease (OR = 0.74, 95% CI 0.55-0.98) and a positive association with the risk of diabetic retinopathy (OR = 1.53, 95% CI 1.08-2.15). Conclusion: The Gln/Glu ratio exhibited a significant association with diabetes, common metabolic parameters, and diabetic complications. These findings shed light on the pivotal role of Gln metabolism in T2D and its associated complications.

Unmet needs in the treatment of type 1 diabetes: why is it so difficult to achieve an improvement in metabolic control?

The development of advanced diabetes technology has permitted persons with type 1 diabetes mellitus to improve metabolic control significantly, particularly with the development of advanced hybrid closed-loop systems which have improved the quality of life by reducing hypoglycemia, decreasing macroangiopathy and microangiopathy-related complications, ameliorating HbA1c and improving glycemic variability. Despite the progression made over the past few decades, there is still significant margin for improvement to be made in terms of attaining appropriate metabolic control. Various factors are responsible for poor glycemic control including inappropriate carbohydrate counting, repeated bouts of hypoglycemia, hypoglycemia unawareness, cutaneous manifestations due to localized insulin use and prolonged use of diabetes technology, psychosocial comorbidities such as eating disorders or 'diabulimia', the coexistence of insulin resistance among people with type 1 diabetes and the inability to mirror physiological endogenous pancreatic insulin secretion appropriately. Hence, the aim of this review is to highlight and overcome the barriers in attaining appropriate metabolic control among people with type 1 diabetes by driving research into adjunctive treatment for coexistent insulin resistance and developing new advanced diabetic technologies to preserve ß cell function and mirror as much as possible endogenous pancreatic functions.

Association of plant-based diet indexes with the metabolomic profile.

Plant-based diets have gained attention for their potential benefits on both human health and environmental sustainability. The objective of this study was to investigate the association of plant-based dietary patterns with the endogenous metabolites of healthy individuals and identify metabolites that may act as mediators of the associations between dietary intake and modifiable disease risk factors. Adherence to plant-based dietary patterns was assessed for 170 healthy adults using plant-based diet indexes (PDI). Individuals with higher healthful PDI had lower BMI and fasting glucose and higher HDL-C, while those with higher unhealthful PDI had higher BMI, triacylglycerol and fasting glucose and lower HDL-C. Unhealthful PDI was associated with higher levels of several amino acids and biogenic amines previously associated with cardiometabolic diseases and an opposite pattern was observed for healthful PDI. Furthermore, healthful PDI was associated with higher levels of glycerophosphocholines containing very long-chain fatty acids. Glutamate, isoleucine, proline, tyrosine, α-aminoadipate and kynurenine had a statistically significant mediation effect on the associations between PDI scores and LDL-C, HDL-C and fasting glucose. These findings contribute to the growing evidence supporting the role of plant-based diets in promoting metabolic health and shed light on the potential mechanisms explaining their beneficial health effects.

An overview of the application and potential mechanism on the triglyceride glucose index with multi-vessel coronary disease.

Multi-vessel coronary disease (MVCD) is a severe form of coronary artery disease (CAD) that significantly increases the risk of acute coronary syndrome (ACS) and heart attacks. The triglyceride glucose (TyG) index is a reliable and convenient marker for insulin resistance (IR). Recent studies have demonstrated its predictive value for CAD in patients with MVCD. This review aims to explore the application of the TyG index in managing MVCD and its underlying pathogenesis to enhance risk stratification and improve therapeutic decision-making.

Association of triglyceride-glucose index with the risk of incident aortic dissection and aneurysm: a large-scale prospective cohort study in UK Biobank.

BACKGROUND: Triglyceride-glucose (TyG) index is an emerging surrogate indicator of insulin resistance, which has been demonstrated as a risk factor for various cardiovascular diseases including coronary syndrome, in-stent restenosis, and heart failure. However, association of TyG index with incident aortic dissection (AD) and aortic aneurysm (AA) remains to be investigated. METHODS: This study included 420,292 participants without baseline AD/AA from the large-scale prospective UK Biobank cohort. The primary outcome was incident AD/AA, comprising AD and AA. Multivariable-adjusted Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were applied to assess the relationship between TyG index and the onset of AD/AA. In addition, the association between TyG index and incident AD/AA was examined within subgroups defined by age, gender, smoking status, drinking status, diabetes, hypertension, and BMI. RESULTS: Over a median follow-up period of 14.8 (14.1, 15.5) years, 3,481 AD/AA cases occurred. The incidence of AD/AA rose along with elevated TyG index. RCS curves showed a linear trend of TyG index with risk of incident AD/AA. TyG index was positively associated with risk of incident AD/AA after adjusting for age, gender, smoking status, drinking status, BMI, hypertension, LDL-c, and HbA1c, with adjusted HRs of 1.0 (reference), 1.20 (95% CI 1.08-1.35), 1.21 (95% CI 1.08-1.35), and 1.30 (95% CI 1.16-1.45) for TyG index quartiles 2, 3, and 4, respectively. Especially, participants in the highest TyG index quartile had highest risk of developing AA, with an adjusted HR of 1.35 (95% CI 1.20-1.52). CONCLUSIONS: TyG index is independently associated with a higher risk of incident AD/AA, indicating the importance of using TyG index for risk assessment of AD/AA, especially for AA.

Acute effects of blood flow restricted aerobic exercise in type 2 diabetes mellitus.

BACKGROUND: This study aimed to compare the acute effects of aerobic exercise performed with blood flow restriction (BFR), a novel method to increase exercise gains, with blood free flow (BFF) conditions in type 2 diabetes mellitus (T2DM). METHODS: Fifteen individuals with T2DM performed BFF and BFR (40% of arterial occlusion pressure) cycling exercises 48 hours apart, at equal intensity (45% heart rate reserve) and duration (38 minutes). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), blood glucose, heart rate, and muscle oxygen saturation (SmO2) were assessed before-after and during exercise sessions. RESULTS: SBP, DBP, and MAP in the overload phase were higher in the BFR group than in the BFF group (P = .009, 0.031, and 0.013, respectively). Changes in blood pressure (∆SBP and ∆DBP) were similar between the BFF and BFR groups (P > .05), whereas ∆MAP differed (P = .016). Changes in blood glucose levels and heart rates were not significantly different between the groups. Although SmO2baseline was lower in the BFR group (P = .049), SmO2min and SmO2max did not differ significantly between the BFF and BFR groups. CONCLUSION: The similar decrease in blood glucose levels between the groups suggests that BFR exercise is favorable in terms of hypoglycemia. The higher blood pressure observed during the BFR exercise remained within safe limits. These results suggest that people with T2DM can safely perform BFR aerobic exercises; however, further studies are required.

Clinical features, biomarkers and diabetic ketoacidosis at diagnosis of type 1 diabetes among children and adolescents in Sana'a, Yemen.

INTRODUCTION: There is little published information on type 1 diabetes (T1D) in children in Yemen. We aimed to identify the clinical characteristics, biomarkers and diabetic ketoacidosis (DKA) at diagnosis of T1D among children and adolescents in a diabetes centre in Sana'a, Yemen. METHODS: A total of 485 children and adolescents aged ≤18 years diagnosed with T1D during the period 2010-2020 were included in the study. The variables investigated were demographic and clinical characteristics, biomarkers, subtypes of T1D, and the risk factors for severe DKA at diagnosis. RESULTS: At diagnosis, children aged <10 years compared with those aged ≥10 years had higher mean plasma glucose (p<0.001) and mean HbA1c (p=0.026), and lower mean C-peptide (pmol/L) (p=0.019), and a higher frequency of DKA at diagnosis than older children (p<0.001). A majority of the study population (383, 79%) presented in DKA . Children aged <10 years presenting with DKA had significantly longer median appraisal interval (p=0.009) and median total diagnosis interval (p=0.025), and significantly lower mean C-peptide (p=0.001) as compared with their peers without DKA. The prevalence of autoantibody-negative 'idiopathic' T1D was 36 (32%) of the total number tested for autoantibody and familial T1D 61 (12.6%) of all the study population. CONCLUSION: In Yemen children aged <10 years with new-onset T1D frequently faced the challenge of a delay in diagnosis and treatment initiation, with severe hyperglycaemia and a higher risk of DKA at diagnosis.

Personalized insulin dosing using reinforcement learning for high-fat meals and aerobic exercises in type 1 diabetes: a proof-of-concept trial.

In type 1 diabetes, high-fat meals require more insulin to prevent hyperglycemia while meals followed by aerobic exercises require less insulin to prevent hypoglycemia, but the adjustments needed vary between individuals. We propose a decision support system with reinforcement learning to personalize insulin doses for high-fat meals and postprandial aerobic exercises. We test this system in a single-arm 16-week study in 15 adults on multiple daily injections therapy (NCT05041621). The primary objective of this study is to assess the feasibility of the novel learning algorithm. This study looks at glucose outcomes and patient reported outcomes. The postprandial incremental area under the glucose curve is improved from the baseline to the evaluation period for high-fat meals (378 ± 222 vs 38 ± 223 mmol/L/min, p = 0.03) and meals followed by exercises (-395 ± 192 vs 132 ± 181 mmol/L/min, p = 0.007). The postprandial time spent below 3.9 mmol/L is reduced after high-fat meals (5.3 ± 1.6 vs 1.8 ± 1.5%, p = 0.003) and meals followed by exercises (5.3 ± 1.2 vs 1.4 ± 1.1%, p = 0.003). Our study shows the feasibility of automatically personalizing insulin doses for high-fat meals and postprandial exercises. Randomized controlled trials are warranted.

Role perceptions and experiences of adult children in remote glucose management for older parents with type 2 diabetes mellitus: a qualitative study.

BACKGROUND: With the advent of the smart phone era, managing blood glucose at home through apps will become more common for older individuals with diabetes. Adult children play important roles in glucose management of older parents. Few studies have explored how adult children really feel about engaging in the glucose management of their older parents with type 2 diabetes mellitus (T2DM) through mobile apps. This study provides insights into the role perceptions and experiences of adult children of older parents with T2DM participating in glucose management through mobile apps. METHODS: In this qualitative study, 16 adult children of older parents with T2DM, who had used mobile apps to manage blood glucose for 6 months, were recruited through purposive sampling. Semi-structured, in-depth, face-to-face interviews to explore their role perceptions and experiences in remotely managing their older parents' blood glucose were conducted. The Consolidated Criteria for Reporting Qualitative Research (COREQ) were followed to ensure rigor in the study. The data collected were analyzed by applying Colaizzi's seven-step qualitative analysis method. RESULTS: Six themes and eight sub-themes were identified in this study. Adult children's perceived roles in glucose management of older parents with T2DM through mobile apps could be categorized into four themes: health decision-maker, remote supervisor, health educator and emotional supporter. The experiences of participation could be categorized into two themes: facilitators to participation and barriers to participation. CONCLUSION: Some barriers existed for adult children of older parents with T2DM participating in glucose management through mobile apps; however, the findings of this study were generally positive. It was beneficial and feasible for adult children to co-manage the blood glucose of older parents. Co-managing blood glucose levels in older parents with T2DM can enhance both adherence rates and confidence in managing blood glucose effectively.

N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus.

BACKGROUND: Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers? METHODS: We examined 162 South Asian and 107 Nordic women in Norway 1-3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP. RESULTS: The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26  (15-38)  vs. 42 (22-66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1-4.4) vs. 1.2 (0.3-4.2) mg/L), IL-6 (2.3 (1.5-3.2) vs. 1.5 (1.5-2.5) pg/mL), leptin (1647 (1176-2480) vs. 1223 (876-2313) pmol/L), and lower adiponectin levels (7.2 (5.3-9.3) vs. 10.0 (7.2-13.5) mg/L) and Matsuda ISI (2.4 (1.7-3.7) vs. 4.2 (2.9-6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP. CONCLUSIONS: NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.

Association between triglyceride-glucose index and gallstones: a cross-sectional study.

This study used data from the National Health and Nutrition Examination Survey (NHANES) to investigate the relationship between the triglyceride-glucose (TyG) index and gallstones. We evaluated the data collected between 2017 to 2020. To evaluate the relationship between TyG index and gallstones, logistic regression analysis, basic characteristics of participants, subgroup analysis, and smooth curve fitting were utilized. The study included 3870 participants over the age of 20 years, 403 of whom reported gallstones, with a prevalence rate of 10.4%. After adjusting for all confounding factors, the risk of gallstones increased by 41% for each unit increase in the TyG index (OR 1.41, 95% CI 1.07, 1.86). The smooth curve fitting also showed a positive correlation between the TyG index and gallstones. Subgroup analysis revealed a significant positive relationship between the TyG index and the risk of gallstones in those aged < 50 years, women, individuals with total cholesterol levels > 200 mg/dL, individuals with body mass index (BMI) > 25, and individuals without diabetes. The risk of gallstones is positively correlated with a higher TyG index. Thus, the TyG index can be used as a predictor of the risk of gallstones.

Optimizing postprandial glucose prediction through integration of diet and exercise: Leveraging transfer learning with imbalanced patient data.

BACKGROUND: In recent years, numerous methods have been introduced to predict glucose levels using machine-learning techniques on patients' daily behavioral and continuous glucose data. Nevertheless, a definitive consensus remains elusive regarding modeling the combined effects of diet and exercise for optimal glucose prediction. A notable challenge is the propensity for observational patient datasets from uncontrolled environments to overfit due to skewed feature distributions of target behaviors; for instance, diabetic patients seldom engage in high-intensity exercise post-meal. METHODS: In this study, we introduce a unique application of Bayesian transfer learning for postprandial glucose prediction using randomized controlled trial (RCT) data. The data comprises a time series of three key variables: continuous glucose levels, exercise expenditure, and carbohydrate intake. For building the optimal model to predict postprandial glucose levels we initially gathered balanced training data from RCTs on healthy participants by randomizing behavioral conditions. Subsequently, we pretrained the model's parameter distribution using RCT data from the healthy cohort. This pretrained distribution was then adjusted, transferred, and utilized to determine the model parameters for each patient. RESULTS: The efficacy of the proposed method was appraised using data from 68 gestational diabetes mellitus (GDM) patients in uncontrolled settings. The evaluation underscored the enhanced performance attained through our method. Furthermore, when modeling the joint impact of diet and exercise, the synergetic model proved more precise than its additive counterpart. CONCLUSION: An innovative application of the transfer-learning utilizing randomized controlled trial data can improve the challenging modeling task of postprandial glucose prediction for GDM patients, integrating both dietary and exercise behaviors. For more accurate prediction, future research should focus on incorporating the long-term effects of exercise and other glycemic-related factors such as stress, sleep.

Bridging the gap between GLP1-receptor agonists and cardiovascular outcomes: evidence for the role of tirzepatide.

Tirzepatide is a new drug targeting glucagon-like peptide 1(GLP1) and gastric inhibitory polypeptide (GIP) receptors. This drug has demonstrated great potential in improving the clinical outcomes of patients with type 2 diabetes. It can lead to weight loss, better glycemic control, and reduced cardiometabolic risk factors. GLP1 receptor agonists have been proven effective antidiabetic medications with possible cardiovascular benefits. Even though they have been proven to reduce the risk of major adverse cardiovascular events, their effectiveness in treating heart failure is unknown. Unlike traditional GLP1 receptor agonists, tirzepatide is more selective for the GIP receptor, resulting in a more balanced activation of these receptors. This review article discusses the possible mechanisms tirzepatide may use to improve cardiovascular health. That includes the anti-inflammatory effect, the ability to reduce cell death and promote autophagy, and also its indirect effects through blood pressure, obesity, and glucose/lipid metabolism. Additionally, tirzepatide may benefit atherosclerosis and lower the risk of major adverse cardiac events. Currently, clinical trials are underway to evaluate the safety and efficacy of tirzepatide in patients with heart failure. Overall, tirzepatide's dual agonism of GLP1 and GIP receptors appears to provide encouraging cardiovascular benefits beyond glycemic control, offering a potential new therapeutic option for treating cardiovascular diseases and heart failure.

Treatment of type 2 diabetes and stress using neuro-emotional technique: case report.

This case report presents a novel, non-pharmacological treatment of Type 2 Diabetes in a 46-year-old male, demonstrating improvements in blood chemistry and psychometric markers after 8 treatments using a Mind-Body Intervention (MBI) called Neuro-Emotional Technique (NET). The patient presented with a diagnosis of Type 2 Diabetes (T2D), pain, psychosocial indicators of stress and anxiety, and a score of 4 on the ACE-Q (Adverse Childhood Experiences Questionnaire) that is consistent with a predisposition to chronic disease and autoimmune disorders. Glucose levels for this patient were above normal levels (typically between 10-15mmol/L where optimal range is between 4-10mmol/L) for at least two months prior to the 4-week NET intervention period, despite the standard use of conventional antidiabetic medications (insulin injections). The patient exhibited numerous indictors of chronic stress that were hypothesised to be underlying his medical diagnosis and a series of 8 NET treatments over a period of 4 weeks was recommended. Psychometric tests and glucose measurements were recorded at baseline (prior to treatment), 4 weeks (at the conclusion of treatment) and at 8 weeks (4 weeks following the conclusion of treatment). Results show that glucose levels were reduced, and self-reported measures of depression, anxiety, stress, distress and pain all decreased from high and extreme levels to within normal ranges after 4 weeks, with ongoing improvement at 8 weeks. McEwen described the concept of allostatic load and the disruptive effects that cumulative stress can have on both mental and physical health. It is hypothesized that NET reduces allostatic load thereby fortifying homeostasis and the salutogenic stress response mechanisms involved in recovery from chronic illness, possibly via the Psycho-Immune-Neuroendocrine (PINE) network. Further studies with larger sample sizes are required to establish whether these results could be extrapolated to a wider population, however the results of this case suggest that it may be beneficial to consider co-management of T2D with an MBI such as NET.