Effects of Metabolic Medicine and Metabolic Surgery on Patient-Reported Outcomes Among Patients with Type 2 Diabetes.

The assessment and management of patient-reported outcomes (PROs) is considered secondary to that of cardiometabolic outcomes. When assessed, health-related quality of life (HRQOL), a PRO, can yield pertinent information that cannot be obtained from cardiometabolic assessments. For instance, physical and mental distress can be quantified and treated. Moreover, treatment convenience and satisfaction can be gaged. Behavioral modification, bariatric surgery, and pharmacotherapy can improve PROs. Typically, HRQOL is responsive to changes in weight. Specifically, weight loss and weight gain are associated with positive and negative changes in quality of life, respectively. In addition, patient satisfaction can be influenced by glycemic control. Therefore, hypoglycemia and hyperglycemic episodes can negatively affect patient satisfaction. When managing type 2 diabetes (T2D), it is important to consider how therapies impact PROs. Generally, changes in clinical outcomes mirror changes in PROs. To best manage T2D, integrating the assessment of PROs with clinical outcomes is needed.

Long-Term Weight Loss Strategies for Obesity.

CONTEXT: Obesity is a chronic disease that is difficult to manage without holistic therapy. The therapeutic armamentarium for obesity primarily consists of 4 forms of therapy: lifestyle modification (ie, diet and exercise), cognitive behavioral therapy, pharmacotherapy, and bariatric surgery. EVIDENCE ACQUISITION: Evidence was consolidated from randomized controlled trials, observational studies, and meta-analyses. EVIDENCE SYNTHESIS: After 2 years, lifestyle interventions can facilitate weight loss that equates to ~5%. Even though lifestyle interventions are plagued by weight regain, they can have substantial effects on type 2 diabetes and cardiovascular disease risk. Although 10-year percentage excess weight loss can surpass 50% after bariatric surgery, weight regain is likely. To mitigate weight regain, instituting a multifactorial maintenance program is imperative. Such a program can integrate diet, exercise, and pharmacotherapy. Moreover, behavioral therapy can complement a maintenance program well. CONCLUSIONS: Obesity is best managed by a multidisciplinary clinical team that integrates diet, exercise, and pharmacotherapy. Bariatric surgery is needed to manage type 2 diabetes and obesity in select patients.

A Review of the Current Evidence: Impact of Metabolic Surgery on Diabetes Outcomes and Obesity-Associated Macrovascular Complications.

PURPOSE OF REVIEW: Type 2 diabetes (T2D) and obesity are comorbidities that generally progress with time even when non-invasive therapies are prescribed. Indeed, weight loss that is achieved with behavioral modification alone is generally inconsistent and often short-lived. In contrast, although patients do experience weight regain with metabolic surgery, they still benefit from a significant net decrease in weight. As a result, T2D remission can be achieved in up to 60% of patients within 2 years after surgery. However, it is unknown if the positive effects of metabolic surgery extend to macrovascular disease risk reduction. RECENT FINDINGS: As noted in four randomized controlled trials (RCTs), Roux-en-Y gastric bypass (RYGB) facilitates partial remission of T2D in about 30% of volunteers 5 years after surgery. Of the four RCTs, only one investigated the effects of sleeve gastrectomy (SG) at 5 years; that study found that the rate of partial relapse was slightly lower with SG (23%). However, observational studies indicate that the gap between RYGB and SG may be larger than that observed in RCTs. In contrast, the rate of full remission is noted infrequently 5 years after SG or RYGB. Metabolic surgery also mitigates macrovascular disease risk as indicated by multiple observational studies. The effects of metabolic surgery on cardiometabolic parameters are clinically meaningful. The weight loss that is facilitated by metabolic surgery reduces the metabolic and inflammatory stress caused by T2D and obesity. In turn, metabolic surgery likely mitigates macrovascular disease risk. Additional evidence from RCTs is needed to substantiate the effects of metabolic surgery on macrovascular disease risk.

Double-blinded, randomized, and controlled study on the effects of canagliflozin after bariatric surgery: A pilot study.

SETTING: Bariatric surgery is indicated for patients diagnosed with obesity and type 2 diabetes. Many patients achieve type 2 diabetes remission soon after bariatric surgery. Even though most maintain good glycemic control, remission is not maintained in all patients, and as a result, some patients may relapse. Type 2 diabetes relapse is common in patients who regain weight; weight regain is prevalent 1 to 2 years after surgery. Additional pharmacotherapy may be required to aid bariatric surgery in fostering weight loss and reducing blood glucose levels. OBJECTIVES: The purpose of this clinical trial was to determine the effects of canagliflozin in participants who initially achieved type 2 diabetes remission but subsequently relapsed. METHODS: The double-blinded, randomized, and prospective study recruited participants (n = 16) roughly 3 years after bariatric surgery. The participants were followed for 6 months. RESULTS: Body mass index (-1.24 kg/m2) and body weight (-3.7 kg) were significantly reduced with canagliflozin therapy versus placebo. There were improvements in body fat composition as denoted by reductions in android (-3.00%) and truncal (-2.67%) fat. Also, there were differences in blood glucose and hemoglobin A1C at 6 months. CONCLUSION: After bariatric surgery, canagliflozin improved weight loss and glycemic outcomes in participants with type 2 diabetes. Canagliflozin also facilitated improvements in body fat composition.

Temporal Dynamics of High-Density Lipoprotein Proteome in Diet-Controlled Subjects with Type 2 Diabetes.

We examined the effect of mild hyperglycemia on high-density lipoprotein (HDL) metabolism and kinetics in diet-controlled subjects with type 2 diabetes (T2D). 2H2O-labeling coupled with mass spectrometry was applied to quantify HDL cholesterol turnover and HDL proteome dynamics in subjects with T2D (n = 9) and age- and BMI-matched healthy controls (n = 8). The activities of lecithin-cholesterol acyltransferase (LCAT), cholesterol ester transfer protein (CETP), and the proinflammatory index of HDL were quantified. Plasma adiponectin levels were reduced in subjects with T2D, which was directly associated with suppressed ABCA1-dependent cholesterol efflux capacity of HDL. The fractional catabolic rates of HDL cholesterol, apolipoprotein A-II (ApoA-II), ApoJ, ApoA-IV, transthyretin, complement C3, and vitamin D-binding protein (all p < 0.05) were increased in subjects with T2D. Despite increased HDL flux of acute-phase HDL proteins, there was no change in the proinflammatory index of HDL. Although LCAT and CETP activities were not affected in subjects with T2D, LCAT was inversely associated with blood glucose and CETP was inversely associated with plasma adiponectin. The degradation rates of ApoA-II and ApoA-IV were correlated with hemoglobin A1c. In conclusion, there were in vivo impairments in HDL proteome dynamics and HDL metabolism in diet-controlled patients with T2D.

Diabetes management before, during, and after bariatric and metabolic surgery.

Metabolic surgery is unrivaled by other therapeutic modalities due to its ability to foster diabetes remission. Metabolic surgery is an integral therapeutic modality in obese and morbidly obese populations because pharmacological and behavioral therapy often fail to effectively manage type II diabetes. However, given the invasiveness of the metabolic surgery relative to behavioral therapy and the need to conform to preparatory and discharge guidelines, patients must adhere to strict nutritional and diabetes management protocols. Also, the pharmacological regimen that is instituted upon discharge is distinct from the preoperative regimen. Oftentimes, the dose for insulin and oral medications are significantly decreased or withdrawn. As time elapses and depending on several factors (e.g., exercise adherence), diabetes control becomes tenuous in a small portion of the patients because there is weight regain and on-going beta cell failure. At this time interval, intensification of diabetes therapy becomes prudent. Indeed, pharmacotherapy from the preoperative to the postoperative phase is labile and may be complex. Therefore, by discussing pharmacology options during the preoperative, perioperative, and postoperative period, the goal is to guide clinician-driven care.

The effects of diabetes therapy on bone: A clinical perspective.

The effects of diabetes and diabetes therapy on bone are less known among clinicians. Traditionally, the emphasis of diabetes therapy has been on reducing cardiovascular risk by facilitating reductions in weight, blood pressure, blood sugar, systemic inflammation, and lipid levels. Now, with ample research demonstrating that patients with diabetes are more susceptible to bone fractures relative to controls, there has been a greater or renewed interest in studying the effects of diabetes therapy on bone. Interestingly, the majority of antidiabetic agents positively affect bone, but a few have detrimental effects. Specifically, although insulin has been demonstrated to be anabolic to bone, the rate of hypoglycemic episodes are increased with exogenous infusion; consequently, there is an increased fall and fracture frequency. Other agents such as thiazolidinediones have more direct negative effects on bone through transcriptional regulation. Even metabolic surgery, to a varying operation-dependent extent, exacerbates bone strength and may heighten fracture rate. The remaining diabetes agents seem to have neutral or positive effects on bone. With the increasing incidence of diabetes, it is more pertinent than ever to fully comprehend the effects of diabetes-related therapeutic modalities.

Prevalence of Anemia in Subjects Randomized into Roux-en-Y Gastric Bypass or Sleeve Gastrectomy.

PURPOSE: Although bariatric surgery fosters heightened excess weight loss values, nutritional deficiencies are prominent; one of the most common being iron deficiency anemia. The purpose is to elucidate the frequency of anemia in Roux-en-Y gastric bypass and sleeve gastrectomy subjects. MATERIALS AND METHODS: A retrospective analysis was conducted, in subjects (N = 100) diagnosed with type II diabetes who were randomized into sleeve gastrectomy or Roux-en-Y gastric bypass and intensive medical therapy. RESULTS: Anemia was more common in female subjects who underwent sleeve gastrectomy-roughly half developed microcytosis at 24 months and thereafter. CONCLUSION: The etiology of anemia appears to be iron-related and precipitated by the female sex. Scant iron supplementation is likely causative. However, anemia of chronic inflammation cannot be discounted as being somewhat causal. Subsequently, the aggregate may have had a synergistic influence.

The therapeutic efficacy of intensive medical therapy in ameliorating high-density lipoprotein dysfunction in subjects with type two diabetes.

BACKGROUND: To determine whether 12 months of intensive medical therapy (IMT) improves HDL functionality parameters in subjects with type II diabetes (T2D). METHODS: Retrospective, randomized, and controlled 12-month IMT intervention trial that enrolled 13-subjects with T2D (age 51- years, fasting glucose 147 mg/dL, body mass index [BMI] 36.5 kg/m(2)) and nine healthy control (46-years, fasting glucose 90 mg/dL, BMI 26.5 kg/m2). Subjects with T2D underwent IMT and HDL functionality measures (pro-inflammatory index of high-density lipoprotein (pHDL)), paraoxonase one (PON1), ceruloplasmin (Cp), and myeloperoxidase (MPO) activity were performed on samples at baseline and at 12-months following IMT. RESULTS: At baseline, pHDL index was significantly higher in subjects with T2D (p < 0.001) and apolipoprotein A-1 levels were significantly lower (p = 0.013) vs. CONTROLS: After 12-months, there was a trend for improved pHDL activity (p = 0.083), as indicated by intent-to-treat analysis, but when the non-adherent subject was omitted (per-protocol), significant attenuations in pHDL activity (p = 0.040) were noted; Δ pHDL activity at 12-months was associated with Δ weight (r = 0.62, p = 0.032) and Δ fasting glucose (r = 0.65, p = 0.022). Moreover, PON1 activity significantly improved (p < 0.001). The aforementioned occurred in association with improvements in inflammatory markers (i.e., C-reactive protein & tumor necrosis factor), hemoglobin A1C, fasting glucose, triglycerides, high-density lipoprotein levels and adipokines. CONCLUSION: IMT ameliorates pHDL index and significantly improves anti-oxidative function, as measured by PON1. Improvements in weight and fasting glucose mediated the decrease in pHDL index. Pharmacological aids and lifestyle modification are required to improve cardiovascular risk factors, subsequent mortality risk, and promote T2D remission. Application of either form of therapy alone may only have relatively miniscule effects on the aforementioned factors, in relation to the aggregate.