***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Reports on the relationship between comorbidity and glycemia control in diabetic patients are conflicting and the method of measuring comorbidity varies widely among studies . The aim of the present study was to evaluate the relationship between diabetes control and comorbidity , taking into account all comorbidities and their severity , in a primary care setting . We performed a retrospective descriptive study based on chart review of 96 r and omly selected type 2 diabetic patients .  Comorbidity was measured with the cumulative illness rating scale ( CIRS ) , an exhaustive comorbidity index . Diabetes was considered as controlled if the mean value of two measurements of glycosylated hemoglobin A ( HbA1c ) was less than 7 % . Taking diabetes control as the dependent variable , its relationship with the CIRS score , age , sex , diabetes duration , and diabetes-related complications was explored . Diabetes control was not significantly related with the CIRS score , age , sex or diabetes severity . Diabetes duration was the only variable significantly related to diabetes control . Our study suggests that comorbidity measured with the CIRS in patients with type 2 diabetes is not a factor that prevents the achievement of a good glycemia control Diabetes mellitus is a leading cause of death in the United States and is associated with microvascular and macrovascular complications . Approximately 29.1 million persons , or 9.3 % of the U.S. population , have type 2 diabetes ( 1 ) . In 2012 , the total direct and indirect costs associated with diabetes in the United States were $ 245 billion ( 1 ) . Markedly elevated glucose levels can result in subacute symptoms , such as polyuria , polydipsia , weight loss , and dehydration . Over time , the metabolic derangements associated with diabetes may lead to vision loss , painful neuropathy or sensory loss , foot ulcers , amputations , myocardial infa rct ions , strokes , and end-stage renal disease . Lowering blood glucose may decrease risk for complications , but lowering strategies come with harms , patient burden , and costs . Blood glucose can be measured in various ways , including the hemoglobin A1c ( HbA1c ; also called glycosylated or glycated hemoglobin ) level , which approximates average blood glucose control over about 3 months . As with all laboratory tests , HbA1c measurements are associated with variability ( 2 ) and can vary further with race and ethnicity ( 35 ) . Guidelines have historically recommended initiation or intensification of pharmacologic therapy to achieve specific HbA1c targets , depending on the population in question . The ideal target that optimally balances benefits and harms remains uncertain . Guidance Statement Focus and Target Population The purpose of this American College of Physicians ( ACP ) guidance statement is to critically review the available guidelines from various organizations and the evidence included therein to assist clinicians in making decisions about targets when using pharmacologic therapy in adults with type 2 diabetes . Recent data suggesting that newer agents reduce cardiovascular morbidity and mortality in high-risk patients with type 2 diabetes have prompted calls for a fundamental shift in diabetes management . Some anticipate that treatment decisions will eventually be based more on cardiovascular risk than achievement of specific HbA1c targets , analogous to recent changes in lipid management . However , for the foreseeable future , glycemic targets will continue to influence management decisions by front-line clinicians ( 6 ) . This statement focuses on the benefits and harms of targeting lower versus higher HbA1c levels and does not cover use of specific medications outside of their use to achieve HbA1c targets . The intended audience is all clinicians , and the target population is nonpregnant adults with type 2 diabetes . Methods The Clinical Guidelines Committee ( CGC ) of ACP develops guidance statements on topics where several conflicting guidelines are available . We provide clinicians with a rigorous review of the guidelines and the evidence they include . We then adopt the clinical recommendations if we agree with their evaluation of benefits and harms or adapt them if changes are needed based on our assessment of the recommendations and evidence . Data Sources and Guideline Selection We search ed the National Guideline Clearinghouse and the Guidelines International Network library ( May 2017 ) for guidelines on recommended HbA1c targets in the treatment of type 2 diabetes in nonpregnant outpatient adults . We included guidelines that were developed by national organizations , were published in English , and targeted the correct population . We review ed titles and abstract s and excluded guidelines that were modified or adapted from other organizations or addressed specific population s ( such as pregnant women or patients with kidney disease ) . Our search yielded guidelines from the National Institute for Health and Care Excellence ( NICE ) ( 7 ) and the Institute for Clinical Systems Improvement ( ICSI ) ( 8) . On the basis of the knowledge and expertise of ACP CGC members , we also selected the following 4 guidelines not identified in either data base at the time of the search but commonly used in clinical practice : the American Association of Clinical Endocrinologists and American College of Endocrinology ( AACE/ACE ) guideline ( 9 ) , the American Diabetes Association ( ADA ) guideline ( 10 ) , the Scottish Intercollegiate Guidelines Network ( SIGN ) guideline ( 11 ) , and the U.S. Department of Veterans Affairs and Department of Defense ( VA/DoD ) guideline ( 12 ) . Quality Assessment Six co authors independently review ed and assessed each guideline using the AGREE II ( Appraisal of Guidelines for Research and Evaluation II ) instrument ( 13 ) . This instrument asks 23 questions in the following 6 domains : scope and purpose , stakeholder involvement , rigor of development , clarity of presentation , applicability , and editorial independence . The authors scored each guideline independently , and the scores were compared ( Appendix Figure and Appendix Table 1 ) . Authors then provided a summary determination of whether they would recommend this guideline for use by recording yes , no , or yes with modifications . Appendix Figure . Mean AGREE II scores for items in each domain across the 6 review ers . Each question was rated on a Likert scale with a minimum of 1 point and a maximum of 7 points . The scores were averaged for each of the 6 review ers . Error bars represent calculated st and ard deviation . AACE/ACE = American Association of Clinical Endocrinologists and American College of Endocrinology ; ADA = American Diabetes Association ; AGREE II = Appraisal of Guidelines for Research and Evaluation II ; GDG = guideline development group ; ICSI = Institute for Clinical Systems Improvement ; NICE = National Institute for Health and Care Excellence ; SIGN = Scottish Intercollegiate Guidelines Network ; VA/DoD = U.S. Department of Veterans Affairs and Department of Defense . Appendix Table 1 . Scaled AGREE II Domain Scores for Each Guideline and Overall Assessment Peer Review The draft guidance statement was peer- review ed through Annals of Internal Medicine and was posted online for comments from ACP Regents and Governors , who represent ACP members at the regional level . The final guidance statement incorporated comments from peer review ers and ACP Regents and Governors . Public Panel Review The development of this guidance statement also included perspectives , values , and preferences of 2 CGC members who represent the public and a 7-member public panel . Summary of Evaluated Guidelines Using the AGREE II Instrument We review ed and rated 6 guidelines ( AACE/ACE [ 9 ] , ADA [ 10 ] , ICSI [ 8 ] , NICE [ 7 ] , SIGN [ 11 ] , and VA/DoD [ 12 ] ) , focusing solely on sections addressing HbA1c targets in patients with type 2 diabetes . Appendix Table 1 shows the detailed scaled domain scores and average quality ratings for each guideline , and the Appendix Figure shows average AGREE II scores for each item in each of the 6 domains . The fundamental difference between high- and low-scoring guidelines was methodology . The 2 lowest-scoring guidelines , AACE/ACE and ADA , scored lowest on stakeholder involvement , applicability , editorial independence , and scientific rigor . A systematic review is the backbone for any trustworthy guideline , but some guidelines might not be based on a systematic review or may not have made the review publicly available ( 14 , 15 ) . Several factors were important in considering guideline quality . For example , although many guidelines described benefits , adverse effects , and the strength and limitations of evidence or linked the evidence to the recommendation , they often inadequately described how they had considered or weighted these factors in developing the final recommendations . The guidelines frequently relied on selective reporting of studies or outcomes and focused on relative versus absolute effects and asymptomatic surrogate measures rather than patient-centered health outcomes . All of the review ed guidelines recommend individualizing HbA1c targets on the basis of patient characteristics , such as comorbid conditions and risk for hypoglycemia ( Appendix ) . The ADA and SIGN guidelines recommend a target of 7 % for the general population , whereas AACE/ACE recommends 6.5 % ( if it can be achieved safely ) . The NICE guideline specifies 6.5 % or 7 % , depending on the patient 's treatment regimen . Both ICSI and VA/DoD recommend target ranges . The ICSI guideline recommends less than 7 % to less than 8 % based on patient factors , whereas the VA/DoD recommends the following target ranges based on life expectancy and comorbid conditions : 6 % to 7 % for patients with a life expectancy greater than 10 to 15 years and no or mild microvascular complications ; 7 % to 8.5 % for those with established microvascular or macrovascular disease , comorbid conditions , or a life expectancy of 5 to 10 years ; and 8 % to 9 % for those with a life expectancy less than 5 years , significant comorbid conditions , advanced complications of diabetes , or difficulties in self-management attributable to mental status , disability , or other factors ( 12 ) . All guidelines recognize that HbA1c targets can be higher in patients with comorbid conditions and limited life expectancy . We looked into the evidence presented in these guidelines , specifically 5 large , long-term r and omized trials with a treat-to-target strategy and corresponding reports on extended follow-up ( 1623 ) . We summarize below the individual studies and result ing benefits and harms . Note that recent studies evaluating the effectiveness and safety of several newer diabetes drugs ( for example , recently approved sodiumglucose cotransporter-2 inhibitors , dipeptidyl peptidase-4 inhibitors , and glucagon-like peptide-1 receptor agonists ) were not considered in guideline sections pertaining to HbA1c targets because these studies were not design ed to evaluate treat-to-target strategies . Therefore , their findings are not described here . Benefits and Harms of Lower HbA1c Targets : Evidence From Clinical Trials Five large , long-term r and omized controlled trials investigated intensive ( achieved HbA1c levels , 6.3 % to 7.4 % ) versus less intensive ( achieved HbA1c levels , 7.3 % to 8.4 % ) OBJECTIVE To determine the relationship between social support and certain indicators of physical and mental wellbeing in older adults with type 2 diabetes . MATERIAL AND METHODS We undertook a population -based cross sectional study of 705 adults with type 2 diabetes from the Instituto Mexicano del Seguro Social ( IMSS ) . Participants were r and omly selected from a list of diabetic patients located in the south of Mexico City . Physical and mental wellbeing were assessed through three indicators : 1 ) Health related quality of life ( HRQL ) ; 2 ) depressive symptomatology , and 3 ) glycemic control . Level of social support level was determined using the The Social Support Health Survey instrument . Multiple linear regression models were used to analyze the independent association of social support with the physical and mental wellbeing indicators , controlling for progression time , diabetes complications , co-morbidity and socio-demographic variables . RESULTS High levels of social support were reported by 64 % of participants . Social support and HRQL increased in direct proportion : the more social support a participant reported the less depressive distress and better fasting glucose levels they showed . The results maintained their significance in the four social support subscales , with the exception of affectionate and emotional or informational support subscales , which were not significantly correlated with fasting glucose . Multiple linear regression analyses showed that better levels of social support are associated with improved HRQL ( beta = 0.12 ) , less incidence of depressive symptoms ( beta = -0.20 ) and lower fasting glucose ( beta = -0.10 ) . CONCLUSIONS Our findings suggest that greater levels of social support may improve certain indicators of physical and mental wellbeing in older adults with type 2 diabetes , regardless of the presence of diabetes complications and other chronic pathologies . Thus , promoting social support for the IMSS ' diabetic patients could be a useful intervention The objective of this study was to develop a prospect ively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies . A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients . The 1-yr mortality rates for the different scores were : " 0 " , 12 % ( 181 ) ; " 1 - 2 " , 26 % ( 225 ) ; " 3 - 4 " , 52 % ( 71 ) ; and " greater than or equal to 5 " , 85 % ( 82 ) . The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up . The percent of patients who died of comorbid disease for the different scores were : " 0 " , 8 % ( 588 ) ; " 1 " , 2 
    Output:
    
This review demonstrates that MM in T2D is associated with higher mortality and hypoglycaemia , whilst evidence regarding the association with other measures of glycaemic control is mixed .