Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony

Chronic obstructive pulmonary disease, metabolic syndrome and diabetes mellitus are common and underdiagnosed medical conditions. It was predicted that chronic obstructive pulmonary disease will be the third leading cause of death worldwide by 2020. The healthcare burden of this disease is even greater if we consider the significant impact of chronic obstructive pulmonary disease on the cardiovascular morbidity and mortality. Chronic obstructive pulmonary disease may be considered as a novel risk factor for new onset type 2 diabetes mellitus via multiple pathophysiological alterations such as: inflammation and oxidative stress, insulin resistance, weight gain and alterations in metabolism of adipokines. On the other hand, diabetes may act as an independent factor, negatively affecting pulmonary structure and function. Diabetes is associated with an increased risk of pulmonary infections, disease exacerbations and worsened COPD outcomes. On the top of that, coexistent OSA may increase the risk for type 2 DM in some individuals. The current scientific data necessitate a greater outlook on chronic obstructive pulmonary disease and chronic obstructive pulmonary disease may be viewed as a risk factor for the new onset type 2 diabetes mellitus. Conversely, both types of diabetes mellitus should be viewed as strong contributing factors for the development of obstructive lung disease. Such approach can potentially improve the outcomes and medical control for both conditions, and, thus, decrease the healthcare burden of these major medical problems.     

Childhood diabetes: a global perspective

Diabetes is an evolving disease, with changing patterns seen in both type 1 and type 2 diabetes. A wide (over 400-fold) variation exists in worldwide incidence rates of type 1 diabetes, with the highest occurring in Finland (over 45 per 100,000 under the age of 15 years) and the lowest in parts of China. In many countries (e.g. in Europe, the Middle East, Australia) the incidence of autoimmune-mediated type 1 diabetes in children <15 years of age has risen by 2-5% per annum. Type 2 diabetes is also increasing rapidly globally and is occurring at a younger age, including in adolescence and childhood. In the USA, approximately one third of newly diagnosed in the adolescent age group is type 2, with up to 20% presenting with ketosis and ketoacidosis. The management of type 2 diabetes is especially difficult in the adolescent age group. Obesity is the single most obvious risk factor for type 2 diabetes. Lifestyle modification programmes starting in childhood are urgently needed and society needs to change its attitudes to childhood nutrition, play and exercise.     

Diabetes prevention--from physiology to implementation.

One of the major challenges today is the development of prevention programs for the clinical practice. Our aim was to develop a concept for a primary diabetes prevention program to be implemented in general health care. Lifestyle intervention addressing diet and exercise has reduced the diabetes risk by up to 58%. Early preventive pharmacological strategies have yielded a diabetes risk reduction of 25-30%. These findings offer a compelling evidence base, but delivery of intervention and care is essential. The challenge therefore is the management of prevention and intervention programs considering scientific aspects and practical requirements during implementation. The Diabetes Prevention Workgroup at the German Diabetes Association has developed a concept for a decentralized prevention program. Based on the results of the prevention studies, the intervention concept consists of a three-step program including identification of the individuals at high risk to develop type 2 diabetes (1), followed by general intervention based on individual choice (2) and maintained continuous intervention for motivation maintenance (3). Structured prevention programs will enable nationwide prevention of diabetes mellitus without consuming large resources. This process will be challenging and time consuming, requiring many partners but resulting in a profitable "health" investment.     

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD): study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. METHODS: This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control).Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice.orControl group: Standard GP care, with referral to secondary care as required, but no access to ICCD.Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (<=7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients. DISCUSSION: Forty-nine practices have been randomized, 1,997 patients have been recruited to the trial, and 20 patients have been recruited to the qualitative study. Results will be available late 2012.Trial registration[ClinicalTrials.gov: Identifier NCT00945204].     

Lifestyle intervention to prevent diabetes: intensive and cost effective

PURPOSE OF REVIEW: Type 2 diabetes is a major cause of morbidity and mortality, and despite treatment advances appears to be increasing in incidence. Since individuals at risk for the disease are usually identifiable in the prediabetic phase of impaired glucose tolerance, early intervention might prevent diabetes and hence its complications from developing. Obesity and sedentary living are powerful determinants of diabetes, and thus lifestyle change is a logical approach to prevention of this disease. Recent clinical trials have now tested the effectiveness of this intervention and form the basis for this review. RECENT FINDINGS: Three clinical trials have demonstrated that, compared with usual care, lifestyle intervention significantly reduced progression rates to diabetes in prediabetic individuals. Each trial incorporated individualization and repeated long-term contacts with facilitators, in which dietary and physical activity goal setting and behavior modification were central themes. Progression to diabetes was reduced in the Da Qing study by approximately 40%, in the Finnish Diabetes Prevention Study by 58% and in the Diabetes Prevention Program by 58%. The Diabetes Prevention Program included a cost-benefit unit that estimated the per capita costs of the lifestyle intervention to exceed that of the usual care group by Dollars 3540, which translated to a cost of Dollars 15,700 per case of diabetes prevented. Lifetime cost-utility analysis demonstrated an overall cost of Dollars 1100 per quality-adjusted life year. SUMMARY: These findings make the case for translation of research findings to healthcare systems. Although there is more to be learned about effective strategies in clinical practice, it seems clear that the intervention needs to incorporate individualization and long-term interaction with trained facilitators.     

Role for fibrate therapy in diabetes: evidence before FIELD

PURPOSE OF REVIEW: Diabetic dyslipidaemia, among the main factors contributing to vascular risk in type 2 diabetes, is characterized by hypertriglyceridaemia, low HDL-cholesterol and increased prevalence of small dense LDL particles. Because fibrates have positive effects on triglycerides, HDL-cholesterol and LDL particle size, they may be an appropriate treatment for diabetic dyslipidaemia. Statins have been shown to diminish significantly the risk for coronary disease in patients with type 2 diabetes, and so what are the real effects of fibrates on cardiovascular risk in type 2 diabetes? RECENT FINDINGS: Although statins reduce the incidence of coronary disease in type 2 diabetes, data from clinical trials demonstrate 'residual' cardiovascular risk in these patients treated with statins. Clinical trials with fibrates show that they are particularly effective in reducing cardiovascular risk in patients with type 2 diabetes/metabolic syndrome and in those exhibiting the lipid abnormalities typical of diabetic dyslipidaemia (elevated triglycerides, low HDL-cholesterol). SUMMARY: Data on the effects of fibrates on cardiovascular risk in diabetes were obtained from subgroup analyses. Thus far, the only study performed specifically in patients with type 2 diabetes is the angiographic Diabetes Atherosclerosis Intervention Study which demonstrated a significant reduction in progression of atherosclerosis in patients receiving fenofibrate, but it was not powered to analyse the effects of fibrates on clinical outcomes. This is why the Fenofibrate Intervention and Event Lowering in Diabetes study is needed; it will provide robust data on the ability of fibrates to reduce cardiovascular risk in patients with type 2 diabetes.     

Diabetes research for developing countries

EAGLES investigations into the specific needs for diabetes research in developing countries, and Europe's potential to support that research [European Union and Diabetes http://ec.europa.eu/health/ph_information/dissemination/diseases/diabetes_en.htm, EU Research on Diabetes http://ec.europa.eu/research/leaflets/diabetes/index_en.html] reach nine major conclusions. In each case, they involve tuning European research to have the greatest impact in the shortest possible time, by understanding and respecting developing countries' conditions of health, politics and economics. Major recommendations arise from the lack of national population-based epidemiology to enable planning and convince political powers of the need for action; from countries' low healthcare budgets, entailing needs for the cheapest possible interventions; from the need to investigate interventions specifically tuned to national circumstances; and finally from the needs for specific local biomedical research, such as studies into the several unique African phenotypes of the disease. The details of our nine recommendations can be seen at the end of the report.     

Molecular docking analysis of beta-caryophyllene with IRS-1, cSrc and Akt

Diabetes mellitus (DM) is a common metabolic illness defined by hyperglycemia caused by insufficient production or absent of pancreatic insulin, with or without concomitant insulin action impairment. Hence, novel problem-solving approaches for assessing early metabolic diseases, notably insulin resistance, are urgently needed. Screening of natural compounds for drug discovery to combat diabetes is common in modern medical research and development. Therefore, it is of interest to document the molecular docking analysis data of beta-Caryophyllene, a naturally occurring sequiterpene with the downstream insulin signaling molecules such as IRS-1, cSrc and Akt for the management of type-2 diabetes. The molecular docking analysis data of beta-caryophyllene with the insulin downstream signaling molecules such as IRS-1, cSrc and Akt reveals its ability and further studies are needed to elucidate its complete mechanism of action against type-2 diabetes.     

American Association of Clinical Endocrinology Consensus Statement: Comprehensive Type 2 Diabetes Management Algorithm – 2023 Update

ObjectiveThis consensus statement provides (1) visual guidance in concise graphic algorithms to assist with clinical decision-making of health care professionals in the management of persons with type 2 diabetes mellitus to improve patient care and (2) a summary of details to support the visual guidance found in each algorithm.MethodsThe American Association of Clinical Endocrinology (AACE) selected a task force of medical experts who updated the 2020 AACE Comprehensive Type 2 Diabetes Management Algorithm based on the 2022 AACE Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan and consensus of task force authors.ResultsThis algorithm for management of persons with type 2 diabetes includes 11 distinct sections: (1) Principles for the Management of Type 2 Diabetes; (2) Complications-Centric Model for the Care of Persons with Overweight/Obesity; (3) Prediabetes Algorithm; (4) Atherosclerotic Cardiovascular Disease Risk Reduction Algorithm: Dyslipidemia; (5) Atherosclerotic Cardiovascular Disease Risk Reduction Algorithm: Hypertension; (6) Complications-Centric Algorithm for Glycemic Control; (7) Glucose-Centric Algorithm for Glycemic Control; (8) Algorithm for Adding/Intensifying Insulin; (9) Profiles of Antihyperglycemic Medications; (10) Profiles of Weight-Loss Medications (new); and (11) Vaccine Recommendations for Persons with Diabetes Mellitus (new), which summarizes recommendations from the Advisory Committee on Immunization Practices of the U.S. Centers for Disease Control and Prevention.ConclusionsAligning with the 2022 AACE diabetes guideline update, this 2023 diabetes algorithm update emphasizes lifestyle modification and treatment of overweight/obesity as key pillars in the management of prediabetes and diabetes mellitus and highlights the importance of appropriate management of atherosclerotic risk factors of dyslipidemia and hypertension. One notable new theme is an emphasis on a complication-centric approach, beyond glucose levels, to frame decisions regarding first-line pharmacologic choices for the treatment of persons with diabetes. The algorithm also includes access/cost of medications as factors related to health equity to consider in clinical decision-making.     

Let's prevent diabetes: study protocol for a cluster randomised controlled trial of an educational intervention in a multi-ethnic UK population with screen detected impaired glucose regulation

ABSTRACT: BACKGROUND: The prevention of type 2 diabetes is a globally recognised health care priority, but there is a lack of rigorous research investigating optimal methods of translating diabetes prevention programmes, based on the promotion of a healthy lifestyle, into routine primary care. The aim of the study is to establish whether a pragmatic structured education programme targeting lifestyle and behaviour change in conjunction with motivational maintenance via the telephone can reduce the incidence of type 2 diabetes in people with impaired glucose regulation (a composite of impaired glucose tolerance and/or impaired fasting glucose) identified through a validated risk score screening programme in primary care. DESIGN: Cluster randomised controlled trial undertaken at the level of primary care practices. Follow-up will be conducted at 12, 24 and 36 months. The primary outcome is the incidence of type 2 diabetes. Secondary outcomes include changes in HbA1c, blood glucose levels, cardiovascular risk, the presence of the Metabolic Syndrome and the cost-effectiveness of the intervention. METHODS: The study consists of screening and intervention phases within 44 general practices coordinated from a single academic research centre. Those at high risk of impaired glucose regulation or type 2 diabetes are identified using a risk score and invited for screening using a 75 g-oral glucose tolerance test. Those with screen detected impaired glucose regulation will be invited to take part in the trial. Practices will be randomised to standard care or the intensive arm. Participants from intensive arm practices will receive a structured education programme with motivational maintenance via the telephone and annual refresher sessions. The study will run from 2009-2014. DISCUSSION: This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme conducted within routine primary care in the United Kingdom. TRIAL REGISTRATION: Clinicaltrials.gov NCT00677937.     

Role of islet amyloid in type 2 diabetes mellitus

Diabetes mellitus is one of the most common metabolic diseases worldwide and its prevalence is rapidly increasing. Due to its chronic nature (diabetes mellitus can be treated but as yet not cured) and its serious complications, it is one of the most expensive diseases with regard to total health care costs per patient. The elevated blood glucose levels in diabetes mellitus are caused by a defect in production and/or secretion of the polypeptide hormone insulin, which normally promotes glucose-uptake in cells. Insulin is produced by the pancreatic 'beta-cells' in the 'islets of Langerhans', which lie distributed within the exocrine pancreatic tissue. In type 2 diabetes mellitus, the initial defect in the pathogenesis of the disease in most of the patients is believed to be 'insulin resistance'. Hyperglycemia (clinically overt diabetes mellitus) will not develop as long as the body is able to produce enough insulin to compensate for the reduced insulin action. When this compensation fails ('beta-cell failure') blood glucose levels will become too high. In this review, we discuss one of the mechanisms that have been implicated in the development of beta-cell failure, i.e. amyloid formation in the pancreatic islets. This islet amyloid is a characteristic histopathological feature of type 2 diabetes mellitus and both in vitro and in vivo studies have revealed that its formation causes death of islet beta-cells. Being a common pathogenic factor in an otherwise heterogeneous disease, islet amyloidosis is an attractive novel target for therapeutic intervention in type 2 diabetes mellitus.     

Evaluating the Cost-Effectiveness of Lifestyle Modification versus Metformin Therapy for the Prevention of Diabetes in Singapore

BackgroundIn Singapore, as diabetes is an increasingly important public health issue, the cost-effectiveness of pursuing lifestyle modification programs and/or alternative prevention strategies is of critical importance for policymakers. While the US Diabetes Prevention Program (DPP) compared weight loss through lifestyle modification with oral treatment of diabetes drug metformin to prevent/delay the onset of type 2 diabetes in pre-diabetic subjects, no data on either the actual or potential cost effectiveness of such a program is available for East or South-east Asian populations. This study estimates the 3-year cost-effectiveness of lifestyle modification and metformin among pre-diabetic subjects from a Singapore health system and societal perspective.MethodologyCost effectiveness was analysed from 2010–2012 using a decision-based model to estimate the rates of getting diabetes, healthcare costs and health-related quality of life. Cost per quality-adjusted life year (QALY) was estimated using costs relevant to the time horizon of the study from Singapore. All costs are expressed in 2012 US dollars.ConclusionBased on adaptation of the DPP data to local conditions, both lifestyle modification and metformin intervention are likely to be cost-effective and worth implementing in Singapore to prevent or delay the onset of type 2 diabetes. However, the cost of lifestyle modification from the societal perspective would have to be reduced in order to match the cost-effectiveness of metformin intervention.     

Genetics of type 2 diabetes: insight from targeted mouse mutants

Diabetes affects millions of people worldwide, and its chronic complications are a leading cause of death in many industrialized countries. In a minority of patients, diabetes is brought about by the auto-immune destruction of insulin-producing pancreatic beta cells (Type 1 diabetes). In the vast majority of patients, diabetes is brought about by a combination of genetic and environmental factors that affect the organism's ability to respond to insulin (Type 2 diabetes). This impairment is due to a complex abnormality involving insulin action at the periphery and insulin production in the beta cell. Genetic factors play a key role in the development of type 2 diabetes. However, the inheritance of diabetes is non-Mendelian in nature, due to genetic heterogeneity, polygenic pathogenesis and incomplete penetrance. For these reasons, many laboratories have developed "designer" mice bearing targeted mutations in genes of the insulin action and insulin secretion pathways in order to develop a better model for the inheritance and pathogenesis of type 2 diabetes. These mutant mice are beginning to challenge established paradigms in the pathogenesis of type 2 diabetes and to shed light onto the genetic interactions underlying its complex inheritance. Here we review recent progress in the field and assess its impact on human studies of the genetics, prevention and treatment of type 2 diabetes.     

Approach to assessing determinants of glucose homeostasis in the conscious mouse

Obesity and type 2 diabetes lessen the quality of life of those afflicted and place considerable burden on the healthcare system. Furthermore, the detrimental impact of these pathologies is expected to persist or even worsen. Diabetes is characterized by impaired insulin action and glucose homeostasis. This has led to a rapid increase in the number of mouse models of metabolic disease being used in the basic sciences to assist in facilitating a greater understanding of the metabolic dysregulation associated with obesity and diabetes, the identification of therapeutic targets, and the discovery of effective treatments. This review briefly describes the most frequently utilized models of metabolic disease. A presentation of standard methods and technologies on the horizon for assessing metabolic phenotypes in mice, with particular emphasis on glucose handling and energy balance, is provided. The article also addresses issues related to study design, selection and execution of metabolic tests of glucose metabolism, the presentation of data, and interpretation of results.     

Ethnic differences in guideline-indicated statin initiation for people with type 2 diabetes in UK primary care, 2006–2019: A cohort study

BackgroundType 2 diabetes is 2–3 times more prevalent in people of South Asian and African/African Caribbean ethnicity than people of European ethnicity living in the UK. The former 2 groups also experience excess atherosclerotic cardiovascular disease (ASCVD) complications of diabetes. We aimed to study ethnic differences in statin initiation, a cornerstone of ASCVD primary prevention, for people with type 2 diabetes.Methods and findingsObservational cohort study of UK primary care records, from 1 January 2006 to 30 June 2019. Data were studied from 27,511 (88%) people of European ethnicity, 2,386 (8%) people of South Asian ethnicity, and 1,142 (4%) people of African/African Caribbean ethnicity with incident type 2 diabetes, no previous ASCVD, and statin use indicated by guidelines. Statin initiation rates were contrasted by ethnicity, and the number of ASCVD events that could be prevented by equalising prescribing rates across ethnic groups was estimated. Median time to statin initiation was 79, 109, and 84 days for people of European, South Asian, and African/African Caribbean ethnicity, respectively. People of African/African Caribbean ethnicity were a third less likely to receive guideline-indicated statins than European people (n/N [%]: 605/1,142 [53%] and 18,803/27,511 [68%], respectively; age- and gender-adjusted HR 0.67 [95% CI 0.60 to 0.76], p < 0.001). The HR attenuated marginally in a model adjusting for total cholesterol/high-density lipoprotein cholesterol ratio (0.77 [95% CI 0.69 to 0.85], p < 0.001), with no further diminution when deprivation, ASCVD risk factors, comorbidity, polypharmacy, and healthcare usage were accounted for (fully adjusted HR 0.76 [95% CI 0.68, 0.85], p < 0.001). People of South Asian ethnicity were 10% less likely to receive a statin than European people (1,489/2,386 [62%] and 18,803/27,511 [68%], respectively; fully adjusted HR 0.91 [95% CI 0.85 to 0.98], p = 0.008, adjusting for all covariates). We estimated that up to 12,600 ASCVD events could be prevented over the lifetimes of people currently affected by type 2 diabetes in the UK by equalising statin prescribing across ethnic groups. Limitations included incompleteness of recording of routinely collected data.ConclusionsIn this study we observed that people of African/African Caribbean ethnicity with type 2 diabetes were substantially less likely, and people of South Asian ethnicity marginally less likely, to receive guideline-indicated statins than people of European ethnicity, even after accounting for sociodemographics, healthcare usage, ASCVD risk factors, and comorbidity. Underuse of statins in people of African/African Caribbean or South Asian ethnicity with type 2 diabetes is a missed opportunity to prevent cardiovascular events.

In a retrospective cohort study, Sophie Eastwood and colleagues investigate the association between ethnicity and statin initiation for people with type 2 diabetes in UK.     

Magnesium metabolism in type 2 diabetes mellitus, metabolic syndrome and insulin resistance

Type 2 diabetes is characterized by cellular and extracellular Mg depletion. Epidemiologic studies showed a high prevalence of hypomagnesaemia and lower intracellular Mg concentrations in diabetic subjects. Insulin and glucose are important regulators of Mg metabolism. Intracellular Mg plays a key role in regulating insulin action, insulin-mediated-glucose uptake and vascular tone. Reduced intracellular Mg concentrations result in a defective tyrosine-kinase activity, post-receptorial impairment in insulin action, and worsening of insulin resistance in diabetic patients. Mg deficit has been proposed as a possible underlying common mechanism of the "insulin resistance" of different metabolic conditions. Low dietary Mg intake is also related to the development of type 2 diabetes. Benefits of Mg supplementation on metabolic profile in diabetic subjects have been found in most, but not all clinical studies, and larger prospective studies are needed to support the potential role of dietary Mg supplementation as a possible public health strategy in diabetes risk.     

Continuous Glucose Monitoring: A Consensus Conference of the American Association of Clinical Endocrinologists and American College of Endocrinology

Objective/Methods: Barriers to continuous glucose monitoring (CGM) use continue to hamper adoption of this valuable technology for the management of diabetes. The American Association of Clinical Endocrinologists and the American College of Endocrinology convened a public consensus conference February 20, 2016, to review available CGM data and propose strategies for expanding CGM access.Results: Conference participants agreed that evidence supports the benefits of CGM in type 1 diabetes and that these benefits are likely to apply whenever intensive insulin therapy is used, regardless of diabetes type. CGM is likely to reduce healthcare resource utilization for acute and chronic complications, although real-world analyses are needed to confirm potential cost savings and quality of life improvements. Ongoing technological advances have improved CGM accuracy and usability, but more innovations in human factors, data delivery, reporting, and interpretation are needed to foster expanded use. The development of a standardized data report using similar metrics across all devices would facilitate clinician and patient understanding and utilization of CGM. Expanded CGM coverage by government and private payers is an urgent need.Conclusion: CGM improves glycemic control, reduces hypoglycemia, and may reduce overall costs of diabetes management. Expanding CGM coverage and utilization is likely to improve the health outcomes of people with diabetes.Abbreviations:A1C = glycated hemoglobinAACE = American Association of Clinical EndocrinologistsACE = American College of EndocrinologyASPIRE = Automation to Simulate Pancreatic Insulin ResponseCGM = continuous glucose monitoringHRQOL = health-related quality of lifeICER = incremental cost-effectiveness ratioJDRF = Juvenile Diabetes Research FoundationMARD = mean absolute relative differenceMDI = multiple daily injectionsQALY = quality-adjusted life yearsRCT = randomized, controlled trialSAP = sensor-augmented pumpSMBG = self-monitoring of blood glucoseSTAR = Sensor-Augmented Pump Therapy for A1C ReductionT1D = type 1 diabetesT2D = type 2 diabetes     

Do Variants Associated with Susceptibility to Pancreatic Cancer and Type 2 Diabetes Reciprocally Affect Risk?

ObjectivesAlthough type 2 diabetes mellitus is a known risk factor for pancreatic cancer, the existence of shared genetic susceptibility is largely unknown. We evaluated whether any reported genetic risk variants of either disease found by genome-wide association studies reciprocally confer susceptibility.MethodsData that were generated in previous genome-wide association studies (GENEVA Type 2 Diabetes; PanScan) were obtained through the National Institutes of Health database of Genotypes and Phenotypes (dbGaP). Using the PanScan datasets, we tested for association of 38 variants within 37 genomic regions known to be susceptibility factors for type 2 diabetes. We further examined whether type 2 diabetes variants predispose to pancreatic cancer risk stratified by diabetes status. Correspondingly, we examined the association of fourteen pancreatic cancer susceptibility variants within eight genomic regions in the GENEVA Type 2 Diabetes dataset.ResultsFour plausible associations of diabetes variants and pancreatic cancer risk were detected at a significance threshold of p = 0.05, and one pancreatic cancer susceptibility variant was associated with diabetes risk at threshold of p = 0.05, but none remained significant after correction for multiple comparisons.ConclusionCurrently identified GWAS susceptibility variants are unlikely to explain the potential shared genetic etiology between Type 2 diabetes and pancreatic cancer.     

Transcultural Diabetes Care in The United States – A Position Statement by the American Association of Clinical Endocrinologists

The American Association of Clinical Endocrinologists (AACE) has created a transculturalized diabetes chronic disease care model that is adapted for patients across a spectrum of ethnicities and cultures. AACE has conducted several transcultural activities on global issues in clinical endocrinology and completed a 3-city series of conferences in December 2017 that focused on diabetes care for ethnic minorities in the U.S. Proceedings from the “Diabetes Care Across America” series of transcultural summits are presented here. Information from community leaders, practicing health care professionals, and other stakeholders in diabetes care is analyzed according to biological and environmental factors. Four specific U.S. ethnicities are detailed: African Americans, Latino/Hispanics, Asian Americans, and Native Americans. A core set of recommendations to culturally adapt diabetes care is presented that emphasizes culturally appropriate terminology, transculturalization of white papers, culturally adapting clinic infrastructure, flexible office hours, behavioral medicine—especially motivational interviewing and building trust—culturally competent nutritional messaging and health literacy, community partnerships for care delivery, technology innovation, clinical trial recruitment and retention of ethnic minorities, and more funding for scientific studies on epigenetic mechanisms of cultural impact on disease expression. It is hoped that through education, research, and clinical practice enhancements, diabetes care can be optimized in terms of precision and clinical outcomes for the individual and U.S. population as a whole.Lay AbstractThe American Association of Clinical Endocrinologists (AACE) has created a diabetes care model for patients of different backgrounds. AACE led meetings in New York, Houston, and Miami with health care professionals and community leaders to improve diabetes care. Information from these meetings looked at biological and environmental diabetes risks. Four American patient groups were studied: African Americans, Latinos, Asian Americans, and Native Americans. Diabetes care should use culturally appropriate language and search for better ways to apply science and clinic design. Talking to patients more clearly can improve their diabetes control. There are many other needed changes in the American health care system discussed in this paper. It is hoped that through better education, research, and practice, diabetes care can be improved for the entire U.S. population. This means that important differences among patients' ethnic and cultural backgrounds are addressed.Executive Summary

• Cultural adaptation of evidence-based recommendations is a necessary component of optimal diabetes care.
• Biological factors that contribute to the pathophysiology of diabetes vary according to race and ethnicity and can be affected by social determinants that vary with culture.
• The “Transcultural Diabetes Nutrition Algorithm” was developed in 2010 to optimize diabetes nutrition care globally and represents a validated methodology where evidence-based recommendations from a source culture can be adapted and implemented in a different culture using a toolkit.
• The 2015 AACE Pan-American Workshop examined diabetes care in 9 Latin American nations and concluded that there should only be one level of diabetes care for a population and that level should be “excellent;” also, that A1C measurements should be utilized and that more educational and nutritional options are needed to optimize diabetes care.
• The “Diabetes Care Across America – A Series of Transcultural Summits” was an AACE program conducted in 2017 in New York, Houston, and Miami to examine cultural factors that influence diabetes care domestically; the findings of this program are presented here.
• The African American, Hispanic/Latino, Asian American, and Native American populations are each comprised of different ancestries, anthropometrics/body compositions and physical appearances, and cultures and degrees of acculturation, with a significant evidence base that associates specific gene variants with specific phenotypic traits affecting diabetes care.
• For each ethno-cultural population, health messaging and diabetes care will need to consider issues of potential distrust of health care professionals, history of discrimination, religious practices, food preferences, attitudes toward physical activity, and despite the full range of socio-economics, the impact of poverty on engagement, self-monitoring, adherence with lifestyle and medical recommendations, and recruitment for clinical trials.
• Diabetes care should be as precise as possible, incorporating clinical trial evidence that best reflects the ethno-cultural attributes of a specific patient, with particular emphasis on cardiovascular disease risk mitigation, technology to assess the effects of eating patterns on glycemic status, adjusting traditional eating patterns to more healthy options that are still acceptable to the patient, flexibility in lifestyle and medication recommendations that take into account cultural factors, and the utilization of community-based resources to improve implementation.
• Pragmatic first steps to prepare a diabetes practice for an ethno-culturally diverse patient population include: learning more about biological-cultural interactions; gaining experience with lifestyle and behavioral medicine, especially motivational interviewing; creating a safe and immersive clinical environment; incorporating translation services, social prescribing, wearable technologies, web-based resources, and community engagement; and establishing referral networks with clinical trialists in diabetes research to improve recruitment of different populations.

ABSTRACTAbbreviations: A1C = hemoglobin A1c; AACE = American Association of Clinical Endocrinologists; ABCD = adiposity-based chronic disease; BMI = body mass index; CPA = clinical practice algorithm; CPG = clinical practice guideline; DBCD = dysglycemia-based chronic disease; DPP = Diabetes Prevention Program; GWAS = genome-wide association study; HCP = health care professional(s); IHS = Indian Health Service; LDL = low-density lipoprotein; MetS = metabolic syndrome; T2D = type 2 diabetes mellitus; tDNA = transcultural Diabetes Nutrition Algorithm; TG = triglyceride; WC = waist circumference