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Efficacy of a pharmacist-managed diabetes clinic in high-risk diabetes patients, a randomized controlled trial - "Pharm-MD" : Impact of clinical pharmacists in diabetes care.
Halalau, A, Sonmez, M, Uddin, A, Karabon, P, Scherzer, Z, Keeney, S
BMC endocrine disorders. 2022;(1):69
Abstract
BACKGROUND Diabetes mellitus affects 13% of American adults. To address the complex care requirements necessary to avoid diabetes-related morbidity, the American Diabetes Association recommends utilization of multidisciplinary teams. Research shows pharmacists have a positive impact on multiple clinical diabetic outcomes. METHODS Open-label randomized controlled trial with 1:1 assignment that took place in a single institution resident-run outpatient medicine clinic. Patients 18-75 years old with type 2 diabetes mellitus and most recent HbA1c ≥9% were randomized to standard of care (SOC) (continued with routine follow up with their primary provider) or to the SOC + pharmacist-managed diabetes clinic PMDC group (had an additional 6 visits with the pharmacist within 6 months from enrollment). Patients were followed for 12 months after enrollment. Data collected included HbA1c, lipid panel, statin use, blood pressure control, immunization status, and evidence of diabetic complications (retinopathy, nephropathy, neuropathy). Intention-to-treat and per-protocol analysis were performed. RESULTS Forty-four patients were enrolled in the SOC + PMDC group and 42 patients in the SOC group. Average decrease in HbA1c for the intervention compared to the control group at 6 months was - 2.85% vs. -1.32%, (p = 0.0051). Additionally, the odds of achieving a goal HbA1c of ≤8% at 6 months was 3.15 (95% CI = 1.18, 8.42, p = 0.0222) in the intervention versus control group. There was no statistically significant difference in the remaining secondary outcomes measured. CONCLUSIONS Addition of pharmacist managed care for patients with type 2 diabetes mellitus is associated with significant improvements in HbA1c compared with standard of care alone. Missing data during follow up limited the power of secondary outcomes analyses. TRIAL REGISTRATION ClinicalTrials.gov , ID: NCT03377127 ; first posted on 19/12/2017.
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Impact of Sodium-Glucose Co-Transporter 2 Inhibitors on Cardiac Protection.
Wu, VC, Li, YR, Wang, CY
International journal of molecular sciences. 2021;(13)
Abstract
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been approved as a new class of anti-diabetic drugs for type 2 diabetes mellitus (T2DM). The SGLT2 inhibitors reduce glucose reabsorption through renal systems, thus improving glycemic control in all stages of diabetes mellitus, independent of insulin. This class of drugs has the advantages of no clinically relevant hypoglycemia and working in synergy when combined with currently available anti-diabetic drugs. While improving sugar level control in these patients, SGLT2 inhibitors also have the advantages of blood-pressure improvement and bodyweight reduction, with potential cardiac and renal protection. In randomized control trials for patients with diabetes, SGLT2 inhibitors not only improved cardiovascular and renal outcomes, but also hospitalization for heart failure, with this effect extending to those without diabetes mellitus. Recently, dynamic communication between autophagy and the innate immune system with Beclin 1-TLR9-SIRT3 complexes in response to SGLT2 inhibitors that may serve as a potential treatment strategy for heart failure was discovered. In this review, the background molecular pathways leading to the clinical benefits are examined in this new class of anti-diabetic drugs, the SGLT2 inhibitors.
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The role of the gut microbiome and its metabolites in metabolic diseases.
Wu, J, Wang, K, Wang, X, Pang, Y, Jiang, C
Protein & cell. 2021;(5):360-373
Abstract
It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases, while in recent years, accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic diseases, including obesity, type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular disease and so on. Numerous microorganisms dwell in the gastrointestinal tract, which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances, thus acting as a link between the gut microbiome and its host. The gut microbiome is shaped by host genetics, immune responses and dietary factors. The metabolic and immune potential of the gut microbiome determines its significance in host health and diseases. Therefore, targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near future. This review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut microbiome-derived metabolites and the pathogenesis of many metabolic diseases. Furthermore, recent advances in improving metabolic diseases by regulating the gut microbiome will be discussed.
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The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease.
Kiernan, K, MacIver, NJ
Frontiers in immunology. 2020;:622468
Abstract
Leptin is a critical mediator of the immune response to changes in overall nutrition. Leptin is produced by adipocytes in proportion to adipose tissue mass and is therefore increased in obesity. Despite having a well-described role in regulating systemic metabolism and appetite, leptin displays pleiotropic actions, and it is now clear that leptin has a key role in influencing immune cell function. Indeed, many immune cells have been shown to respond to leptin directly via the leptin receptor, resulting in a largely pro-inflammatory phenotype. Understanding the role of adipose-tissue derived mediators in inflammation is critical to determining the pathophysiology of multiple obesity-associated diseases, such as type 2 diabetes, autoimmune disease, and infection. This review, therefore, focuses on the latest data regarding the role of leptin in modulating inflammation.
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Immune complex formation in human diabetic retina enhances toxicity of oxidized LDL towards retinal capillary pericytes.
Fu, D, Yu, JY, Wu, M, Du, M, Chen, Y, Abdelsamie, SA, Li, Y, Chen, J, Boulton, ME, Ma, JX, et al
Journal of lipid research. 2014;(5):860-9
Abstract
Recently it has been shown that levels of circulating oxidized LDL immune complexes (ox-LDL-ICs) predict the development of diabetic retinopathy (DR). This study aimed to investigate whether ox-LDL-ICs are actually present in the diabetic retina, and to define their effects on human retinal pericytes versus ox-LDL. In retinal sections from people with type 2 diabetes, costaining for ox-LDL and IgG was present, proportionate to DR severity, and detectable even in the absence of clinical DR. In contrast, no such staining was observed in retinas from nondiabetic subjects. In vitro, human retinal pericytes were treated with native LDL, ox-LDL, and ox-LDL-IC (0-200 mg protein/l), and measures of viability, receptor expression, apoptosis, endoplasmic reticulum (ER) and oxidative stresses, and cytokine secretion were evaluated. Ox-LDL-IC exhibited greater cytotoxicity than ox-LDL toward retinal pericytes. Acting through the scavenger (CD36) and IgG (CD64) receptors, low concentrations of ox-LDL-IC triggered apoptosis mediated by oxidative and ER stresses, and enhanced inflammatory cytokine secretion. The data suggest that IC formation in the diabetic retina enhances the injurious effects of ox-LDL. These findings offer new insights into pathogenic mechanisms of DR, and may lead to new preventive measures and treatments.
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Variation in macro and trace elements in progression of type 2 diabetes.
Siddiqui, K, Bawazeer, N, Joy, SS
TheScientificWorldJournal. 2014;:461591
Abstract
Macro elements are the minerals of which the body needs more amounts and are more important than any other elements. Trace elements constitute a minute part of the living tissues and have various metabolic characteristics and functions. Trace elements participate in tissue and cellular and subcellular functions; these include immune regulation by humoral and cellular mechanisms, nerve conduction, muscle contractions, membrane potential regulations, and mitochondrial activity and enzyme reactions. The status of micronutrients such as iron and vanadium is higher in type 2 diabetes. The calcium, magnesium, sodium, chromium, cobalt, iodine, iron, selenium, manganese, and zinc seem to be low in type 2 diabetes while elements such as potassium and copper have no effect. In this review, we emphasized the status of macro and trace elements in type 2 diabetes and its advantages or disadvantages; this helps to understand the mechanism, progression, and prevention of type 2 diabetes due to the lack and deficiency of different macro and trace elements.
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Diabetic ketoacidosis: an overlooked child killer in sub-Saharan Africa?
Murunga, AN, Owira, PM
Tropical medicine & international health : TM & IH. 2013;(11):1357-64
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Abstract
The true incidence of diabetic ketoacidosis (DKA) in sub-Saharan Africa is unknown but unlike in the Western countries, DKA is also uniquely frequent among type 2 diabetes patients of African origin. Increased hyperglycaemia and hepatic ketogenesis lead to osmotic diuresis, dehydration and tissue hypoxia. Acute complications of DKA include cerebral oedema, which may be compounded by malnutrition, parasitic and microbial infections with rampant tuberculosis and HIV. Overlapping symptoms of these conditions and misdiagnosis of DKA contribute to increased morbidity and mortality. Inability of the patients to afford insulin treatment leads to poor glycemic control as some patients seek alternative treatment from traditional healers or use herbal remedies further complicating the disease process. Standard treatment guidelines for DKA currently used may not be ideal as they are adapted from those of the developed world. Children presenting with suspected DKA should be screened for comorbidities which may complicate fluid and electrolyte replacement therapy protocol. Patient rehabilitation should take into account concurrent treatment for infectious conditions to avoid possible life-threatening drug interactions. We recommend that health systems in sub-Saharan Africa leverage the Expanded Immunization Programme or TB/HIV/AIDS programmes, which are fairly well entrenched to support diabetes services.
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The double burden.
Faurholt-Jepsen, D
Danish medical journal. 2013;(7):B4673
Abstract
One third of the world's population is latently infected with Mycobacterium tuberculosis, and with the lifestyle changes succeeding the on-going urbanization, populations already burdened by tuberculosis are experiencing a dramatic increase in chronic diseases, with diabetes being a serious challenge. Tuberculosis and diabetes are not only becoming co-existing diseases. In fact, the diseases interact, and there is evidence to suggest that especially diabetes disease increases the susceptibility for developing active tuberculosis disease. Furthermore, it is plausible that tuberculosis leads to, either transient or permanent, impairment of the glucose metabolism, which ultimately will turn into diabetes. A number of studies from the Americas, Europe, Asia, and, most lately, from sub-Saharan Africa have reported strong association between tuberculosis and diabetes; on average, the estimated risk of active tuberculosis is thrice as high among people with diabetes. The study from sub-Saharan Africa was conducted in Tanzania and is the basis of this thesis. Based on available evidence on the association between tuberculosis and diabetes, the primary aim of the study was to assess the role of diabetes for tuberculosis risk, manifestations, treatment outcomes and survival in a Tanzanian population of tuberculosis patients and non-tuberculosis neighbourhood controls. The study was conducted in Mwanza City in northern Tanzania, with a population exceeding half a million inhabitants, with tuberculosis and HIV being common infections in the region, but with little knowledge about the prevalence of diabetes. We recruited newly diagnosed pulmonary tuberculosis patients from spring 2006 and continuously till the fall 2009, with all participating in a nutritional intervention running in parallel with the medical tuberculosis treatment. All participants underwent diabetes and HIV testing as well as a series of measurements such as anthropometric, clinical and paraclinical parameters. The population was followed up during treatment (2 and 5 months) to assess treatment outcome as well as after one year to assess their survival status. Based on data from 1,250 tuberculosis patients and 350 neighbourhood controls, we found that 38 and 21%, respectively, had impaired glycaemia, and that the prevalence of diabetes was 17 and 9% among tuberculosis patients and controls, respectively. This difference in prevalence between patients and controls was equivalent to an adjusted odds ratio of more than four, indicating a strong association between tuberculosis and diabetes. Furthermore, we found that diabetes was associated with tuberculosis among both participants with or without HIV co-infection. Despite the strong association, diabetes had only moderate clinical implications when the tuberculosis patients initiated the tuberculosis treatment; the patients with diabetes co-morbidity had a minor elevation in the immune response and more frequently reported to have fever. Furthermore, diabetes did not seem to delay time to sputum conversion during treatment. Nevertheless, diabetes co-morbidity led to impaired treatment outcome with slower recovery of weight and haemoglobin and a more than four times higher mortality rate within the initial phase of tuberculosis treatment. In conclusion, in the African region, the double burden of tuberculosis and diabetes is becoming a major health problem. Although the tuberculosis incidence has stabilized during the last decade, the increasing incidence of diabetes will possibly interfere with tuberculosis control and may, consequently, make the tuberculosis incidence increase again. Future research strategies should focus on enhanced diagnostic tools to identify tuberculosis patients with diabetes co-morbidity, and on the role of disease-disease, drug-disease and drug-drug interactions between tuberculosis and diabetes diseases and treatments.
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Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years.
Kashyap, P, Farrugia, G
Gut. 2010;(12):1716-26
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Abstract
Diabetic gastroparesis is a disorder that occurs in both type 1 and type 2 diabetes. It is associated with considerable morbidity among these patients and with the resultant economic burden on the health system. It is primarily a disease seen in middle-aged women, although the increased predisposition in women still remains unexplained. Patients often present with nausea, vomiting, bloating, early satiety and abdominal pain. The pathogenesis of this complex disorder is still not well understood but involves abnormalities in multiple interacting cell types including the extrinsic nervous system, enteric nervous system, interstitial cells of Cajal (ICCs), smooth muscles and immune cells. The primary diagnostic test remains gastric scintigraphy, although other modalities such as breath test, capsule, ultrasound, MRI and single photon emission CT imaging show promise as alternative diagnostic modalities. The mainstay of treatment for diabetic gastroparesis has been antiemetics, prokinetics, nutritional support and pain control. In recent years, gastric stimulation has been used in refractory cases with nausea and vomiting. As we better understand the pathophysiology, newer treatment modalities are emerging with the aim of correcting the underlying defect. In this review, what has been learned about diabetic gastroparesis in the past 5 years is highlighted. The epidemiology, pathogenesis, diagnosis and treatment of diabetic gastroparesis are reviewed, focusing on the areas that are still controversial and those that require more studies. There is also a focus on advances in our understanding of the cellular changes that underlie development of diabetic gastroparesis, highlighting new opportunities for targeted treatment.
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Sleep duration, lifestyle intervention, and incidence of type 2 diabetes in impaired glucose tolerance: The Finnish Diabetes Prevention Study.
Tuomilehto, H, Peltonen, M, Partinen, M, Lavigne, G, Eriksson, JG, Herder, C, Aunola, S, Keinänen-Kiukaanniemi, S, Ilanne-Parikka, P, Uusitupa, M, et al
Diabetes care. 2009;(11):1965-71
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Abstract
OBJECTIVE Both short and long sleep duration have frequently been found to be associated with an increased risk for diabetes. The aim of the present exploratory analysis was to examine the association between sleep duration and type 2 diabetes after lifestyle intervention in overweight individuals with impaired glucose tolerance in a 7-year prospective follow-up. RESEARCH DESIGN AND METHODS A total of 522 individuals (aged 40-64 years) were randomly allocated either to an intensive diet-exercise counseling group or to a control group. Diabetes incidence during follow-up was calculated according to sleep duration at baseline. Sleep duration was obtained for a 24-h period. Physical activity, dietary intakes, body weight, and immune mediators (C-reactive protein and interleukin-6) were measured. RESULTS Interaction between sleep duration and treatment group was statistically significant (P = 0.003). In the control group, the adjusted hazard ratios (HRs) (95% CI) for diabetes were 2.29 (1.38-3.80) and 2.74 (1.67-4.50) in the sleep duration groups 9-9.5 h and >or=10 h, respectively, compared with for that of the 7-8.5 h group. In contrast, sleep duration did not influence the incidence of diabetes in the intervention group; for sleep duration groups 9-9.5 h and >or=10 h, the adjusted HRs (95% CI) were 1.10 (0.60-2.01) and 0.73 (0.34-1.56), respectively, compared with that in the reference group (7-8.5 h sleep). Lifestyle intervention resulted in similar improvement in body weight, insulin sensitivity, and immune mediator levels regardless of sleep duration. CONCLUSIONS Long sleep duration is associated with increased type 2 diabetes risk. Lifestyle intervention with the aim of weight reduction, healthy diet, and increased physical activity may ameliorate some of this excess risk.