In the United States, rural areas have a higher burden of type 2 diabetes (T2DM) compared to urban areas. However, there is limited information on risk factors and interventions that improve the ...primary prevention and management of T2DM in rural areas. To synthesize current knowledge on T2DM in rural areas and to guide healthcare providers and policy makers, we reviewed five scientific databases and the grey literature over the last decade (2010–2020). We described classification systems for rurality and the T2DM burden based on rurality and region (West, South, Midwest, and Northeast). We highlighted risk factors for T2DM in rural compared to urban areas, and summarized interventions to screen and manage T2DM based on opportunistic screening, T2DM self‐management, community‐based initiatives, as well as interventions targeting comorbidities and T2DM. Several studies identified the co‐existence of T2DM and depression/psychological symptoms, which could reduce adherence to non‐pharmacologic and pharmacologic management of T2DM. We highlighted the role of technology in education and counselling of patients with geographic and financial barriers to accessing care, which is exacerbated by the SARS‐CoV‐2 coronavirus disease‐19 pandemic. We identified knowledge gaps and next steps in improving T2DM care in rural areas. There is an urgent need for interventions tailored to rural areas given that rural Americans currently experience a disproportionate burden of T2DM and are encumbered by its associated morbidity, mortality, and loss in economic productivity.
The Oral Minimal Model Method COBELLI, Claudio; MAN, Chiara Dalla; TOFFOLO, Gianna ...
Diabetes (New York, N.Y.),
04/2014, Letnik:
63, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The simultaneous assessment of insulin action, secretion, and hepatic extraction is key to understanding postprandial glucose metabolism in nondiabetic and diabetic humans. We review the oral minimal ...method (i.e., models that allow the estimation of insulin sensitivity, β-cell responsivity, and hepatic insulin extraction from a mixed-meal or an oral glucose tolerance test). Both of these oral tests are more physiologic and simpler to administer than those based on an intravenous test (e.g., a glucose clamp or an intravenous glucose tolerance test). The focus of this review is on indices provided by physiological-based models and their validation against the glucose clamp technique. We discuss first the oral minimal model method rationale, data, and protocols. Then we present the three minimal models and the indices they provide. The disposition index paradigm, a widely used β-cell function metric, is revisited in the context of individual versus population modeling. Adding a glucose tracer to the oral dose significantly enhances the assessment of insulin action by segregating insulin sensitivity into its glucose disposal and hepatic components. The oral minimal model method, by quantitatively portraying the complex relationships between the major players of glucose metabolism, is able to provide novel insights regarding the regulation of postprandial metabolism.
The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, ...diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers.
The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development.
This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes.
This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.
Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by ...denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans. Given the role of Dipeptidyl Peptidase-4 (DPP4) in glucose homeostasis, we further demonstrate that DMAb-treated participants have a significant reduction in circulating DPP4 and increase in Glucagon-like peptide (GLP)-1 levels as compared to the placebo-treated group, and also that type 2 diabetic patients treated with DMAb show significant reductions in HbA1c as compared to patients treated either with bisphosphonates or calcium and vitamin D. Thus, our results identify several coupling factors in humans and uncover osteoclast-derived DPP4 as a potential link between bone remodeling and energy metabolism.
Aims/hypothesis
Shift-work is associated with circadian rhythm disruption and an increased risk of obesity and type 2 diabetes. We sought to determine the effect of rotational shift-work on glucose ...metabolism in humans.
Methods
We studied 12 otherwise healthy nurses performing rotational shift-work using a randomised crossover study design. On each occasion, participants underwent an isotope-labelled mixed meal test during a simulated day shift and a simulated night shift, enabling simultaneous measurement of glucose flux and beta cell function using the oral minimal model. We sought to determine differences in fasting and postprandial glucose metabolism during the day shift vs the night shift.
Results
Postprandial glycaemic excursion was higher during the night shift (381±33 vs 580±48 mmol/l per 5 h,
p
<0.01). The time to peak insulin and C-peptide and nadir glucagon suppression in response to meal ingestion was also delayed during the night shift. While insulin action did not differ between study days, the beta cell responsivity to glucose (59±5 vs 44±4 × 10
−9
min
−1
;
p
<0.001) and disposition index were decreased during the night shift.
Conclusions/interpretation
Impaired beta cell function during the night shift may result from normal circadian variation, the effect of rotational shift-work or a combination of both. As a consequence, higher postprandial glucose concentrations are observed during the night shift.
The interaction between the upper gastrointestinal tract and the endocrine system is important in the regulation of metabolism and of weight. The gastrointestinal tract has a heterogeneous cellular ...content and comprises a variety of cells that elaborate paracrine and endocrine mediators that collectively form the entero-endocrine system. The advent of therapy that utilizes these pathways as well as the association of bariatric surgery with diabetes remission has (re-)kindled interest in the role of the gastrointestinal tract in glucose homeostasis. In this review, we will use the changes wrought by bariatric surgery to provide insights into the various gut-pancreas interactions that maintain weight, regulate satiety, and limit glucose excursions after meal ingestion.
The contribution of elevated glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism after Roux-en-Y gastric bypass (RYGB) has been the subject of uncertainty. We used exendin-9,39, a ...competitive antagonist of GLP-1, to examine glucose metabolism, islet hormone secretion, and gastrointestinal transit in subjects after RYGB and in matched control subjects. Subjects were studied in the presence or absence of exendin-9,39 infused at 300 pmol/kg/min. Exendin-9,39 resulted in an increase in integrated postprandial glucose concentrations post-RYGB (3.6 ± 0.5 vs. 2.0 ± 0.4 mol/6 h, P = 0.001). Exendin-9,39 decreased insulin concentrations (12.3 ± 2.2 vs. 18.1 ± 3.1 nmol/6 h, P = 0.002) and the β-cell response to glucose (Total, 13 ± 1 vs. 11 ± 1 × 10(-9) min(-1), P = 0.01) but did not alter the disposition index (DI). In control subjects, exendin-9,39 also increased glucose (2.2 ± 0.4 vs. 1.7 ± 0.3 mol/6 h, P = 0.03) without accompanying changes in insulin concentrations, resulting in an impaired DI. Post-RYGB, acceleration of stomach emptying during the first 30 min by exendin-9,39 did not alter meal appearance, and similarly, suppression of glucose production and stimulation of glucose disappearance were unaltered in RYGB subjects. These data indicate that endogenous GLP-1 has effects on glucose metabolism and on gastrointestinal motility years after RYGB. However, it remains uncertain whether this explains all of the changes after RYGB.
Patients with type 2 diabetes mellitus are at an increased risk of adverse cardiovascular events compared to those without diabetes. The timing, relative to disease onset, and degree of glycemic ...control that reduces the risk of adverse cardiovascular events remains uncertain. Coronary microvascular dysfunction is prevalent in patients with type 2 diabetes mellitus and is linked to adverse cardiovascular events. We assessed the association between endothelial-dependent and endothelial-independent coronary microvascular dysfunction and glycemic control in patients presenting with chest pain and nonobstructive coronary disease at angiography.
Patients presenting with chest pain and found to have non-obstructive CAD (stenosis < 40%) at angiography underwent an invasive assessment of endothelial-independent and endothelial -dependent microvascular function. Endothelial-independent microvascular function was assessed by comparing the coronary flow velocity, measured using a Doppler guidewire, in response to intracoronary infusion of adenosine to calculate the coronary flow reserve ratio in response to adenosine (CFRAdn Ratio). A CFRAdn Ratio ≤ 2.5 was considered abnormal. Endothelial-dependent microvascular function was assessed by measuring the percent change in coronary blood flow in response to intracoronary infusions of acetylcholine (%ΔCBFAch), and microvascular endothelial dysfunction defined as a %ΔCBFAch of ≤ 50%. Patients were classified by normal versus abnormal CFRAdn Ratio and %ΔCBFAch. Measurements of HbA1c and fasting serum glucose were obtained prior to catheterization and compared between groups.
Between 1993 and 2012, 1469 patients (mean age 50.4 years, 35% male) underwent coronary angiography and invasive testing for coronary microvascular dysfunction, of which 129 (8.8%) had type 2 diabetes. Fifty-one (39.5%) had an abnormal %ΔCBFAch and 49 (38.0%) had an abnormal CFRAdn Ratio. Conventional cardiovascular risk factors and cardiovascular or diabetic medication use did not vary significantly between groups. Females with an abnormal CFRAdn Ratio or abnormal %ΔCBFAch had a significantly higher HbA1c compared to patients with a normal CFRAdn Ratio or %ΔCBFAch respectively: HbA1c % (standard deviation) 7.4 (2.1) vs. 6.5 (1.1), p = 0.035 and 7.3 (1.9) vs. 6.4 (1.2), p = 0.022, respectively. Female patients with an abnormal CFRAdn Ratio had significantly higher fasting serum glucose concentrations compared to those with a normal CFRAdn Ratio: fasting serum glucose mg/dL (standard deviation) 144.4 (55.6) vs. 121.9 (28.1), p = 0.035. This was not observed in men. Amongst female diabetics, a higher HbA1c was significantly associated with any coronary microvascular dysfunction both in a univariate and multivariate analysis: odds ratio (95% confidence interval) 1.69 (1.01-2.86) p = 0.049; and a fasting serum glucose > 140 mg/dL was significantly associated with an abnormal CFRAdn Ratio, 4.28 (1.43-12.81).
Poor glycemic control is associated with coronary microvascular dysfunction amongst female diabetics presenting with chest pain and non-obstructive CAD. These findings highlight the importance of sex specific risk stratification models and treatment strategies when managing cardiovascular risk amongst diabetics. Further studies are required to identify additional risk prevention tools and therapies targeting microvascular dysfunction as an integrated index of cardiovascular risk.
Coordinated communication among pancreatic islet cells is necessary for maintenance of glucose homeostasis. In diabetes, chronic exposure to pro-inflammatory cytokines has been shown to perturb β ...cell communication and function. Compelling evidence has implicated extracellular vesicles (EVs) in modulating physiological and pathological responses to β cell stress. We report that pro-inflammatory β cell small EVs (cytokine-exposed EVs cytoEVs) induce β cell dysfunction, promote a pro-inflammatory islet transcriptome, and enhance recruitment of CD8+ T cells and macrophages. Proteomic analysis of cytoEVs shows enrichment of the chemokine CXCL10, with surface topological analysis depicting CXCL10 as membrane bound on cytoEVs to facilitate direct binding to CXCR3 receptors on the surface of β cells. CXCR3 receptor inhibition reduced CXCL10-cytoEV binding and attenuated β cell dysfunction, inflammatory gene expression, and leukocyte recruitment to islets. This work implies a significant role of pro-inflammatory β cell-derived small EVs in modulating β cell function, global gene expression, and antigen presentation through activation of the CXCL10/CXCR3 axis.
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•Pro-inflammatory β-cell small extracellular vesicles (cytoEVs) induce β cell dysfunction•cytoEVs alter the islet transcriptome and enhance leukocyte recruitment to islets•Pro-inflammatory cytoEV cargo (e.g., CXCL10) activates the CXCL10/CXCR3 axis in β cells•CXCR3 blockade attenuates cytoEV-mediated β cell dysfunction and leukocyte recruitment
Javeed et al. demonstrate the importance of pro-inflammatory-exposed β cell-derived extracellular vesicles (cytoEVs) as facilitators of β cell dysfunction and a pro-inflammatory islet microenvironment. Physiological and mechanistic evidence implicates CXCL10/CXCR3 axis activation mediated by cytoEVs and improvements in β cell function upon CXCR3 receptor blockade.
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