Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes.

BACKGROUND: Data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to microvascular and cardiovascular disease outcomes in persons with type 2 diabetes. METHODS: We assessed the comparative effectiveness of four commonly used glucose-lowering medications, added to metformin, in achieving and maintaining a glycated hemoglobin level of less than 7.0% in participants with type 2 diabetes. The randomly assigned therapies were insulin glargine U-100 (hereafter, glargine), glimepiride, liraglutide, and sitagliptin. Prespecified secondary outcomes with respect to microvascular and cardiovascular disease included hypertension and dyslipidemia, confirmed moderately or severely increased albuminuria or an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m2 of body-surface area, diabetic peripheral neuropathy assessed with the Michigan Neuropathy Screening Instrument, cardiovascular events (major adverse cardiovascular events [MACE], hospitalization for heart failure, or an aggregate outcome of any cardiovascular event), and death. Hazard ratios are presented with 95% confidence limits that are not adjusted for multiple comparisons. RESULTS: During a mean 5.0 years of follow-up in 5047 participants, there were no material differences among the interventions with respect to the development of hypertension or dyslipidemia or with respect to microvascular outcomes; the mean overall rate (i.e., events per 100 participant-years) of moderately increased albuminuria levels was 2.6, of severely increased albuminuria levels 1.1, of renal impairment 2.9, and of diabetic peripheral neuropathy 16.7. The treatment groups did not differ with respect to MACE (overall rate, 1.0), hospitalization for heart failure (0.4), death from cardiovascular causes (0.3), or all deaths (0.6). There were small differences with respect to rates of any cardiovascular disease, with 1.9, 1.9, 1.4, and 2.0 in the glargine, glimepiride, liraglutide, and sitagliptin groups, respectively. When one treatment was compared with the combined results of the other three treatments, the hazard ratios for any cardiovascular disease were 1.1 (95% confidence interval [CI], 0.9 to 1.3) in the glargine group, 1.1 (95% CI, 0.9 to 1.4) in the glimepiride group, 0.7 (95% CI, 0.6 to 0.9) in the liraglutide group, and 1.2 (95% CI, 1.0 to 1.5) in the sitagliptin group. CONCLUSIONS: In participants with type 2 diabetes, the incidences of microvascular complications and death were not materially different among the four treatment groups. The findings indicated possible differences among the groups in the incidence of any cardiovascular disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).

Executive Summary: Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

BACKGROUND: Numerous laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. An expert committee compiled evidence-based recommendations for laboratory analysis in patients with diabetes. The overall quality of the evidence and the strength of the recommendations were evaluated. The draft consensus recommendations were evaluated by invited reviewers and presented for public comment. Suggestions were incorporated as deemed appropriate by the authors (see Acknowledgments in the full version of the guideline). The guidelines were reviewed by the Evidence Based Laboratory Medicine Committee and the Board of Directors of the American Association of Clinical Chemistry and by the Professional Practice Committee of the American Diabetes Association. CONTENT: Diabetes can be diagnosed by demonstrating increased concentrations of glucose in venous plasma or increased hemoglobin A1c (Hb A1c) in the blood. Glycemic control is monitored by the patients measuring their own blood glucose with meters and/or with continuous interstitial glucose monitoring devices and also by laboratory analysis of Hb A1c. The potential roles of noninvasive glucose monitoring; genetic testing; and measurement of ketones, autoantibodies, urine albumin, insulin, proinsulin, and C-peptide are addressed. SUMMARY: The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

BACKGROUND: Numerous laboratory tests are used in the diagnosis and management of diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. APPROACH: An expert committee compiled evidence-based recommendations for laboratory analysis in screening, diagnosis, or monitoring of diabetes. The overall quality of the evidence and the strength of the recommendations were evaluated. The draft consensus recommendations were evaluated by invited reviewers and presented for public comment. Suggestions were incorporated as deemed appropriate by the authors (see Acknowledgments). The guidelines were reviewed by the Evidence Based Laboratory Medicine Committee and the Board of Directors of the American Association of Clinical Chemistry and by the Professional Practice Committee of the American Diabetes Association. CONTENT: Diabetes can be diagnosed by demonstrating increased concentrations of glucose in venous plasma or increased hemoglobin A1c (Hb A1c) in the blood. Glycemic control is monitored by the people with diabetes measuring their own blood glucose with meters and/or with continuous interstitial glucose monitoring (CGM) devices and also by laboratory analysis of Hb A1c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of ketones, autoantibodies, urine albumin, insulin, proinsulin, and C-peptide are addressed. SUMMARY: The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.

Weight management in young adults with type 1 diabetes: The advancing care for type 1 diabetes and obesity network sequential multiple assignment randomized trial pilot results.

AIMS: Co-management of weight and glycaemia is critical yet challenging in type 1 diabetes (T1D). We evaluated the effect of a hypocaloric low carbohydrate, hypocaloric moderate low fat, and Mediterranean diet without calorie restriction on weight and glycaemia in young adults with T1D and overweight or obesity. MATERIALS AND METHODS: We implemented a 9-month Sequential, Multiple Assignment, Randomized Trial pilot among adults aged 19-30 years with T1D for ≥1 year and body mass index 27-39.9 kg/m2 . Re-randomization occurred at 3 and 6 months if the assigned diet was not acceptable or not effective. We report results from the initial 3-month diet period and re-randomization statistics before shutdowns due to COVID-19 for primary [weight, haemoglobin A1c (HbA1c), percentage of time below range <70 mg/dl] and secondary outcomes [body fat percentage, percentage of time in range (70-180 mg/dl), and percentage of time below range <54 mg/dl]. Models adjusted for design, demographic and clinical covariates tested changes in outcomes and diet differences. RESULTS: Adjusted weight and HbA1c (n = 38) changed by -2.7 kg (95% CI -3.8, -1.5, P < .0001) and -0.91 percentage points (95% CI -1.5, -0.30, P = .005), respectively, while adjusted body fat percentage remained stable, on average (P = .21). Hypoglycaemia indices remained unchanged following adjustment (n = 28, P > .05). Variability in all outcomes, including weight change, was considerable (57.9% were re-randomized primarily due to loss of <2% body weight). No outcomes varied by diet. CONCLUSIONS: Three months of a diet, irrespective of macronutrient distribution or caloric restriction, resulted in weight loss while improving or maintaining HbA1c levels without increasing hypoglycaemia in adults with T1D.

Did the 2015 USPSTF Abnormal Blood Glucose Recommendations Change Clinician Attitudes or Behaviors? A Mixed-Method Assessment.

BACKGROUND: In 2015, the US Preventive Services Task Force (USPSTF) revised clinical recommendations to more broadly recommend abnormal blood glucose screening and more clearly recommend referral to behavioral interventions for adults with prediabetes. OBJECTIVE: To assess the effects of the 2015 USPSTF recommendation changes on abnormal blood glucose screening and referral to behavioral interventions, and to examine physicians' perceptions of the revised recommendation. DESIGN: We utilized a sequential, dependent mixed-methods triangulation design. PARTICIPANTS: A total of 33,444 patients meeting USPSTF abnormal blood glucose screening criteria within 15 health system-affiliated primary care practices and 20 primary care physicians in North Carolina. MAIN MEASURES: We assessed monthly abnormal blood glucose screening rate and monthly referral rate to behavioral interventions. To estimate trend changes in outcomes, we used segmented linear regression analysis of interrupted time-series data. We gathered physicians' perspectives on the 2015 USPSTF abnormal blood glucose recommendation including awareness of, agreement with, adoption of, and adherence to the recommendation. To analyze qualitative data, we used directed content analysis. KEY RESULTS: There was a slight significant change in trend in abnormal blood glucose screening rates post-recommendation. There was a slight, statistically significant decrease in referral rates to behavioral interventions post-recommendation. Physicians were generally unaware of the revisions to the 2015 USPSTF abnormal blood glucose recommendation; however, once the recommendations were described, physicians agreed with the screening recommendation but felt that the behavioral intervention referral recommendation was hard to implement. CONCLUSION: The 2015 USPSTF abnormal blood glucose guideline had little to no effect on abnormal blood glucose screening or referral to behavioral interventions in North Carolina practices. Potential interventions to improve these rates could include clinical decision tools embedded in the electronic health record and better referral systems for community-based diabetes prevention programs.

The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycaemia, behavioural considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that healthcare professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors. Graphical abstract.

The linearized disposition index augments understanding of treatment effects in diabetes.

The disposition index, calculated by multiplying measures of insulin secretion and insulin sensitivity, is widely applied as a sensitivity-adjusted measure of insulin secretion. We have recently shown that linearizing the underlying relationship uniquely permits identification of terms relating to maximal insulin secretion capacity and the secretion-coupling relationship, with both terms separately contributing to differences in the secretion-sensitivity relationship across gradations of glycemia. Here, we demonstrate the application of this linearized equation to the evaluation of treatment-induced changes in the insulin secretion-sensitivity relationship. We applied a combination of repeated-measures multivariate linear regression (evaluating treatment-induced changes in the joint relationship of insulin sensitivity and secretion) plus mixed-model repeated measures (evaluating treatment effects on maximal secretion capacity and on the secretion-sensitivity coupling slope) and compared against a usual application of the disposition index calculated from the same measurements. This novel approach allows a more informative description of treatment-induced changes compared with the usual disposition index, including isolating the source of change within the mutually adjusted relationship and identifying treatment-induced changes in the secretion-sensitivity coupling slope and in maximal insulin secretion. Application of this linearized approach provides an expanded understanding of treatment-induced changes in the insulin sensitivity-secretion relationship.NEW & NOTEWORTHY The linearized insulin secretion-sensitivity relationship allows separate evaluation of the secretion-sensitivity slope and of maximal insulin secretion. Here, we demonstrate the application of this methodology to the evaluation of clinical trial data, showing that it provides an expanded understanding of treatment-induced changes compared with the disposition index.

Race and gender differences in abnormal blood glucose screening and clinician response to prediabetes: A mixed-methods assessment.

The projected three-fold increase in diabetes burden by 2060 in the United States will affect certain race and gender groups disproportionately. The objective of this mixed-methods study was to assess differences in prediabetes screening and clinician response to prediabetes by patient race and gender. We utilized data from 18,742 patients seen between 11/1/15 and 4/30/17 who met criteria for blood glucose screening by the 2015 US Preventive Service Task Force recommendation and had at least one visit to a primary care practice within a large, academic health system located in North Carolina. We utilized generalized estimating equations with logistic regression to assess race and gender differences in two outcomes: prediabetes screening and clinician response to prediabetes. We conducted twenty in-depth interviews (October 2018-May 2019) with physicians to assess their approach to screening for and treating prediabetes. Black patients had 11% higher odds (95% CI:1.02-1.20) of being screened for prediabetes than White patients. Men had 19% higher odds (95% CI:1.09-1.30) of being screened for prediabetes than women. There were no significant differences in clinician response to prediabetes by patient race or gender. Qualitatively, physicians reported a non-systematic approach to prediabetes screening and follow-up care related to: 1) System-level barriers to screening and treatment; 2) Implicit bias; 3) Patient factors; and 4) Physician preferences for prediabetes treatment. Targeted risk-based screening for prediabetes along with increased treatment for prediabetes are critical for preventing diabetes and reducing diabetes-related disparities.

Poor appetite and overeating reported by adults in Australia during the coronavirus-19 disease pandemic: a population-based study.

OBJECTIVE: As a result of the coronavirus-19 disease (COVID-19) pandemic, Australia adopted emergency measures on 22 March 2020. This study reports the effect of the COVID-19 lockdown on appetite and overeating in Australian adults during the first month of emergency measures. DESIGN: This study reports analysis of data from the population-based, self-completed survey. The main outcome measure was an item from the Patient Health Questionnaire 9 asking: 'Over the past 2 weeks, how often have you been bothered by poor appetite or overeating?'. Data on sociodemographic factors, symptoms of anxiety and depression, and the impact of COVID-19 and lockdown were also collected. Multivariable logistic regression was used to examine associations with poor appetite or overeating. SETTING: An anonymous online survey available from 3 April to 2 May 2020. PARTICIPANTS: A total of 13 829 Australian residents aged 18 years or over. RESULTS: The weighted prevalence of being bothered by poor appetite or overeating in the past 2 weeks was 53·6 %, with 11·6 % (95 % CI 10·6, 12·6) of the cohort reporting poor appetite or overeating nearly every day. High levels of anxiety, concern about contracting COVID-19, being in lockdown with children and reporting a severe impact of the lockdown were associated with increased odds of poor appetite or overeating. CONCLUSIONS: Given the widespread prevalence of being bothered by poor appetite or overeating, universal public health interventions to address emotion-focused or situational eating during periods of lockdown may be appropriate.

Findings From a National Diabetes Survey: Highlighting Progress and Opportunities for Diabetes Prevention and Care.

The National Diabetes Education Program (NDEP) implemented periodic deployment of the NDEP National Diabetes Survey (NNDS) in 2006 to collect data on diabetes-related knowledge, attitudes, and behaviors among U.S. adults with diabetes and on risk-reduction attitudes and behaviors among people at risk for type 2 diabetes. Because of similarities in the nationally representative samples of the past three surveys, trends between 2011 and 2016 can be assessed. We present key findings of the 2016 NNDS, focusing on areas of interest to diabetes educators. The 2016 NNDS identified both progress and gaps. Eighty-nine percent of people with diabetes are aware of the A1C test, and disparities by race and ethnicity are narrowing. Awareness of the link between cardiovascular disease and diabetes has plateaued at 75% of respondents. Most people with diabetes do not feel comfortable managing hyper- or hypoglycemia (65 and 60%, respectively), and 60-69% report some level of diabetes distress. Among people without diabetes, awareness of personal risk of type 2 diabetes has increased from 30% in 2011 to 45% in 2016. A diagnosis of prediabetes significantly increases awareness of personal risk of diabetes (65% of people with prediabetes vs. 45% of those at risk), likelihood of receiving counseling about reducing risk (45 vs. 11%), and likelihood of taking action to reduce risk (71 vs. 52%). However, 33% of people without diabetes report not planning to take action to lower their risk of type 2 diabetes. The 2016 NNDS results suggest that outreach and educational efforts have increased knowledge about diabetes and diabetes risk, but also point to the need for more education and support for people with diabetes and those at risk.

Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial.

BACKGROUND: The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity. METHODS: We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant's body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2-11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220. FINDINGS: We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7-1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8-1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0-10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21-0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study. INTERPRETATION: Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.

Survey of Reproductive Experiences and Outcomes of Cancer Survivors Who Stored Reproductive Material Before Treatment.

STUDY QUESTION: What are the reproductive experiences and outcomes of people who store reproductive material before cancer treatment? SUMMARY ANSWER: Of respondents who had tried to achieve pregnancy since completing cancer treatment almost all had succeeded, in most cases through natural conception. WHAT IS KNOWN ALREADY: People of reproductive age who are diagnosed with cancer can cryopreserve reproductive material to guard against the adverse effects on fertility of gonadotoxic treatment. Little is known about the reproductive outcomes of people who undergo fertility preservation before cancer treatment. STUDY DESIGN, SIZE, DURATION: Cross-sectional survey. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women and men who had stored reproductive material before cancer treatment at two private and one public fertility clinics up to June 2014 and were at least 18 years old at the time were identified from medical records and invited to complete an anonymous questionnaire about their reproductive experiences. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 870 potential respondents 302 (171 female and 131 male) returned completed questionnaires yielding a response rate of 34.5% (39.5% and 29.7% for female and male respondents, respectively). Current age was similar for women and men (37.2 years) but men had been diagnosed with cancer significantly earlier in life than women (28.2 versus 30.3 years, P = 0.03). Almost two-thirds of respondents wished to have a child or another child in the future, some of whom knew that they were unable to. One in ten respondents was a parent before the cancer diagnosis and around one-third had had a child since diagnosis or was pregnant (or a partner in pregnancy) at the time of the survey. Of those who had tried to conceive since completing cancer treatment (N = 119) 84% (79% of women and 90% of men) had had a child or were pregnant (or a partner in pregnancy). Most of the pregnancies since the diagnosis of cancer occurred after natural conception (58/100, 58%). Of the 22 women (13% of all women) and 35 men (27% of all men) who had used their stored reproductive material four women (18%) and 28 men (80%) had had a child or were pregnant or a partner in pregnancy at the time of completing the survey. The most commonly stated reason for not using the stored material was not being ready to try for a baby. LIMITATIONS, REASON FOR CAUTION: The relatively low response rate, particularly among men, means that participation bias may have influenced the findings. As type of cancer was self-reported and we did not ask questions about respondents' cancer treatments, it is not possible to link reproductive outcomes to type of cancer or cancer treatment. Also, there is no way of comparing the sample with the populations they were drawn from as data on reproductive outcomes of people who store reproductive material before cancer treatment are not collected routinely. This might have led to over- or underestimates of the reproductive experiences and outcomes reported in this paper. WIDER IMPLICATIONS OF THE FINDINGS: The findings add to the limited evidence about the reproductive outcomes of this growing group of people and can be used to inform the advice given to those contemplating fertility preservation in the context of cancer. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the National Health and Medical Research Council (APP1042347). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Endometriosis and fertility: women's accounts of healthcare.

STUDY QUESTION: What do women with endometriosis recall being told about their fertility by their healthcare providers? SUMMARY ANSWER: Women recalled being given varied information and advice, and gave examples of empathic and individualized care from doctors but also reported opportunities for enhancing clinical practice. WHAT IS KNOWN ALREADY: There is evidence of an association between endometriosis and infertility. However, the strength of this association and the mechanisms that underlie it are not yet known nor are the implications for optimum healthcare. STUDY DESIGN, SIZE, DURATION: This study used in-depth cross-sectional qualitative research methods. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged at least 18 years who lived in Victoria, Australia, and who had been surgically diagnosed with endometriosis were invited to participate in in-depth interviews about their experience of endometriosis. Twenty-six women of diverse backgrounds and experiences of endometriosis were interviewed from January to September 2014. Interviews were transcribed and analysed thematically using a data-driven approach. MAIN RESULTS AND THE ROLE OF CHANCE: All women encountered medical professionals who were aware of the association between endometriosis and infertility, and who were proactive in ensuring fertility was addressed within endometriosis care. Women recalled being given varied, often conflicting, information about the consequences for their fertility of an endometriosis diagnosis. While some recounted positive experiences with the way their doctor communicated with them about endometriosis and fertility, all women reported adverse experiences such as receiving insufficient or inappropriate information or having their doctor prioritize their fertility over other aspects of their care, including quality of life and symptom relief, without first consulting them. LIMITATIONS, REASONS FOR CAUTION: The perspectives of the women's doctors were not sought. The findings may not translate to settings that differ from a predominantly Anglo-Saxon country with both universal public and private healthcare systems. WIDER IMPLICATIONS OF THE FINDINGS: Women's fertility needs and priorities differ for many reasons; there can be no 'one size fits all' approach to care. Women may benefit most from endometriosis care in which they are first asked about their fertility needs and preferences and in which medical uncertainty is acknowledged. STUDY FUNDING/COMPETING INTERESTS: K.Y. receives a scholarship from the National Health and Medical Research Council and Australian Rotary Health. J.F. is supported by a Monash Professional Fellowship and the Jean Hailes Professional Fellowship which is funded by Perpetual Trustees Pty Ltd. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Profound defects in ß-cell function in screen-detected type 2 diabetes are not improved with glucose-lowering treatment in the Early Diabetes Intervention Program (EDIP).

BACKGROUND: Few studies have measured the ability of interventions to affect declining ß-cell function in screen-detected type 2 diabetes. The Early Diabetes Intervention Programme (ClinicalTrials.gov NCT01470937) was a randomized study based on the hypothesis that improving postprandial glucose excursions with acarbose would slow the progression of fasting hyperglycaemia in screen-detected type 2 diabetes. In the Early Diabetes Intervention Programme, the effect of acarbose plus lifestyle advice on progression of fasting hyperglycaemia over a 5-year period was not greater than that of placebo. However, there was an early glucose-lowering effect of the trial. The objective of the current secondary analysis was to describe ß-cell function changes in response to glucose lowering. METHODS: Participants were overweight adult subjects with screen-detected type 2 diabetes. ß-cell function was measured using hyperglycaemic clamps and oral glucose tolerance testing. The primary outcome was the change in ß-cell function from baseline to year 1, the time point where the maximal glucose-lowering effect was seen. RESULTS: At baseline, participants exhibited markedly impaired first-phase insulin response. Despite significant reductions in weight, fasting plasma glucose (PG) and 2-h PG, there was no clinically significant improvement in the first-phase insulin response. Late-phase insulin responses declined despite beneficial glycaemic effects of interventions. CONCLUSIONS: Insulin secretion is already severely impaired in early, screen-detected type 2 diabetes. Effective glucose-lowering intervention with acarbose was not sufficient to improve insulin secretion or halt the decline of ß-cell function.

Intracranial pressure monitoring, cerebral perfusion pressure estimation, and ICP/CPP-guided therapy: a standard of care or optional extra after brain injury?

Measurement of intracranial pressure (ICP) and mean arterial pressure (MAP) is used to derive cerebral perfusion pressure (CPP) and to guide targeted therapy of acute brain injury (ABI) during neurointensive care. Here we provide a narrative review of the evidence for ICP monitoring, CPP estimation, and ICP/CPP-guided therapy after ABI. Despite its widespread use, there is currently no class I evidence that ICP/CPP-guided therapy for any cerebral pathology improves outcomes; indeed some evidence suggests that it makes no difference, and some that it may worsen outcomes. Similarly, no class I evidence can currently advise the ideal CPP for any form of ABI. 'Optimal' CPP is likely patient-, time-, and pathology-specific. Further, CPP estimation requires correct referencing (at the level of the foramen of Monro as opposed to the level of the heart) for MAP measurement to avoid CPP over-estimation and adverse patient outcomes. Evidence is emerging for the role of other monitors of cerebral well-being that enable the clinician to employ an individualized multimodality monitoring approach in patients with ABI, and these are briefly reviewed. While acknowledging difficulties in conducting robust prospective randomized studies in this area, such high-quality evidence for the utility of ICP/CPP-directed therapy in ABI is urgently required. So, too, is the wider adoption of multimodality neuromonitoring to guide optimal management of ICP and CPP, and a greater understanding of the underlying pathophysiology of the different forms of ABI and what exactly the different monitoring tools used actually represent.

Managing hyponatremia in neurosurgical patients.

Hyponatremia is common in neurosurgical patients and is associated with significant morbidity and mortality. Despite significant research efforts to date, we still lack a complete understanding of the pathophysiological mechanisms underlying hyponatremia in this patient setting. The purpose of this narrative review is to provide an overview of our understanding of hyponatremia in neurosurgical patients, the management principles, and the challenges that arise for the physician managing such patients. Challenges to managing these patients include: the fact that the syndrome of inappropriate antidiuretic hormone (SIADH) and cerebral salt wasting (CSW) may actually represent parts of the same clinical spectrum; the difficulty in distinguishing between CSW, SIADH, and the hypovolemic hyponatremia resulting from a normal pressure natriuresis caused by the administration of large fluid volumes; and that hyponatremia can result from therapeutic agents used in these patients. Treatment of the hyponatremia depends on factors such as the underlying neurosurgical pathology, whether the hyponatremia is acute or chronic, and the fluid status of the patient. Hypertonic saline is a common treatment option. Other treatment options include vasopressin 2 receptor antagonists and steroids, but large prospective trials are required to suitably assess their efficacy and safety in the neurosurgical setting. Of all the challenges that hyponatremia in neurosurgical patients present, perhaps the most pressing is the need for a better understanding of the underlying pathophysiological mechanisms. Only once we begin to better understand this can more efficacious treatments be directed against hyponatremia in this important population.

Women's reflections on fertility and motherhood after breast cancer and its treatment.

Breast cancer and its treatment have complex ramifications for women of reproductive age, including reduced fertility. With the aim of increasing understanding of what it means to women to manage fertility and motherhood in the years after a diagnosis of breast cancer, in-depth qualitative interviews were conducted with 10 women aged 26-45 years, living in Victoria, Australia, who had been diagnosed with breast cancer aged 25-41. Transcripts were analysed thematically and interpreted within narrative theory. Six themes linking breast cancer to fertility and motherhood were identified: diagnosis as a pivotal life event, robbed of time and choice, significance of fertility, being a mother, narrative justification, and life after breast cancer treatment. Women without children described a preoccupying sorrow about lost fertility. Women's accounts yielded evidence of narrative meaning-making, including justifying their decisions and actions in relation to survival, treatment and fertility, and coping with adversity by developing consoling plots. Breast cancer, fertility and reproductive health are inter-linked in diverse ways which have immediate and long-term consequences. Even if women are receiving optimum fertility management, it is evident that some women of reproductive age will need continuing post-cancer care to manage and ameliorate ramifications of diminished or lost fertility.

Point-of-Care HbA1c in Clinical Practice: Caveats and Considerations for Optimal Use.

Hemoglobin A1c (A1C) is widely used for the diagnosis and management of diabetes. Accurate measurement of A1C is necessary for optimal clinical value. Assay standardization has markedly improved the accuracy and consistency of A1C testing. Devices to measure A1C at point of care (POC) are commercially available, allowing rapid results when the patient is seen. In this review, we describe how standardization of A1C testing was achieved, leading to high-quality results in clinical laboratories. We address the use of POC A1C testing in clinical situations and summarize the advantages and disadvantages of POC A1C testing. We emphasize the importance of considering the limitations of these devices and following correct testing procedures to ensure that accurate A1C results are obtained for optimal care of patients.