Showing papers in "Diabetes Care in 2017"

Diabetic Neuropathy: A Position Statement by the American Diabetes Association

Abstract: Diabetic neuropathies are the most prevalent chronic complications of diabetes. This heterogeneous group of conditions affects different parts of the nervous system and presents with diverse clinical manifestations. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons: 1. Diabetic neuropathy is a diagnosis of exclusion. Nondiabetic neuropathies may be present in patients with diabetes and may be treatable by specific measures. 2. A number of treatment options exist for symptomatic diabetic neuropathy. 3. Up to 50% of diabetic peripheral neuropathies may be asymptomatic. If not recognized and if preventive foot care is not implemented, patients are at risk for injuries to their insensate feet. 4. Recognition and treatment of autonomic neuropathy may improve symptoms, reduce sequelae, and improve quality of life. Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy (DSPN) and diabetic autonomic neuropathies, particularly cardiovascular autonomic neuropathy (CAN), are by far the most studied (1–4). There are several atypical forms of diabetic neuropathy as well (1–4). Patients with prediabetes may also develop neuropathies that are similar to diabetic neuropathies (5–10). Table 1 provides a comprehensive classification scheme for the diabetic neuropathies. View this table: Table 1 Classification for diabetic neuropathies Due to a lack of treatments that target the underlying nerve damage, prevention is the key component of diabetes care. Screening for symptoms and signs of diabetic neuropathy is also critical in clinical practice, as it may detect the earliest stages of neuropathy, enabling early intervention. Although screening for rarer atypical forms of diabetic neuropathy may be warranted, DSPN and autonomic neuropathy are the most common forms encountered in practice. The strongest available evidence regarding treatment pertains to these forms. This Position Statement is based on several recent technical reviews, to which the reader is referred for detailed discussion …

International Consensus on Use of Continuous Glucose Monitoring

Abstract: Measurement of glycated hemoglobin (HbA1c) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA1c testing and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA1c measurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes.

Diabetic Retinopathy: A Position Statement by the American Diabetes Association.

Abstract: Diabetic retinopathy diagnostic assessment and treatment options have improved dramatically since the 2002 American Diabetes Association Position Statement (1). These improvements include the widespread adoption of optical coherence tomography to assess retinal thickness and intraretinal pathology and wide-field fundus photography to reveal clinically silent microvascular lesions. Treatment of diabetic macular edema is now achieved by intravitreous injection of anti–vascular endothelial growth factor agents, and the same drugs are now used for proliferative diabetic retinopathy. Improvements in medications and devices for the systemic therapy of diabetes have also improved the ability of patients to optimize their metabolic control. This Position Statement incorporates these recent developments for the use of physicians and patients. Diabetic retinopathy is a highly specific neurovascular complication of both type 1 and type 2 diabetes, the prevalence of which strongly correlates to both the duration of diabetes and level of glycemic control. A pooled meta-analysis involving 35 studies conducted worldwide from 1980 to 2008 estimated global prevalence of any diabetic retinopathy and proliferative diabetic retinopathy (PDR) among patients to be 35.4% and 7.5%, respectively (2). Diabetic retinopathy is the most frequent cause of new cases of blindness among adults aged 20–74 years in developed countries. Glaucoma, cataracts, and other disorders of the eye occur earlier and more frequently in people with diabetes. In addition to diabetes duration, factors that increase the risk of or are associated with retinopathy include chronic hyperglycemia (3,4), nephropathy (5), hypertension (6), and dyslipidemia (7). Intensive diabetes management with the goal of achieving near-normoglycemia has been shown in large prospective randomized studies to prevent and/or delay the onset and progression of diabetic retinopathy (8,9). Lowering blood pressure has been shown to decrease retinopathy progression in people with type 2 diabetes, although tight targets (systolic blood pressure <120 mmHg) do …

How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial

Abstract: OBJECTIVE In the BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial involving 7,020 patients with type 2 diabetes and established cardiovascular (CV) disease, empagliflozin given in addition to standard of care reduced the risk of CV death by 38% versus placebo (hazard ratio [HR] 0.62 [95% CI 0.49, 0.77]). This exploratory mediation analysis assesses the extent to which treatment group differences in covariates during the trial contributed to CV death risk reduction with empagliflozin. RESEARCH DESIGN AND METHODS Effects of potential mediators, identified post hoc, on the HR for CV death with empagliflozin versus placebo were analyzed by Cox regression models, with treatment group adjusted for the baseline value of the variable and its change from baseline or updated mean (i.e., considering all prior values), each as a time-dependent covariate. HRs were compared with a model without adjustment for covariates. Multivariable analyses also were performed. RESULTS Changes in hematocrit and hemoglobin mediated 51.8% and 48.9%, respectively, of the effect of empagliflozin versus placebo on the risk of CV death on the basis of changes from baseline, with similar results in analyses on the basis of updated means. Smaller mediation effects (maximum 29.3%) were observed for uric acid, fasting plasma glucose, and HbA 1c . In multivariable models, which incorporated effects of empagliflozin on hematocrit, fasting glucose, uric acid, and urine albumin:creatinine ratio, the combined changes from baseline provided 85.2% mediation, whereas updated mean analyses provided 94.6% mediation of the effect of empagliflozin on CV death. CONCLUSIONS In this exploratory analysis from the EMPA-REG OUTCOME trial, changes in markers of plasma volume were the most important mediators of the reduction in risk of CV death with empagliflozin versus placebo.

Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut.

Abstract: OBJECTIVE Recent studies suggest the beneficial effects of metformin on glucose metabolism may be microbially mediated. We examined the association of type 2 diabetes, metformin, and gut microbiota in community-dwelling Colombian adults. On the basis of previous research, we hypothesized that metformin is associated with higher levels of short-chain fatty acid (SCFA)–producing and mucin-degrading microbiota. RESEARCH DESIGN AND METHODS Participants were selected from a larger cohort of 459 participants. The present analyses focus on the 28 participants diagnosed with diabetes—14 taking metformin— and the 84 participants without diabetes who were matched (3-to-1) to participants with diabetes by sex, age, and BMI. We measured demographic information, anthropometry, and blood biochemical parameters and collected fecal samples from which we performed 16S rRNA gene sequencing to analyze the composition and structure of the gut microbiota. RESULTS We found an association between diabetes and gut microbiota that was modified by metformin use. Compared with participants without diabetes, participants with diabetes taking metformin had higher relative abundance of Akkermansia muciniphila, a microbiota known for mucin degradation, and several gut microbiota known for production of SCFAs, including Butyrivibrio, Bifidobacterium bifidum, Megasphaera, and an operational taxonomic unit of Prevotella. In contrast, compared with participants without diabetes, participants with diabetes not taking metformin had higher relative abundance of Clostridiaceae 02d06 and a distinct operational taxonomic unit of Prevotella and a lower abundance of Enterococcus casseliflavus. CONCLUSIONS Our results support the hypothesis that metformin shifts gut microbiota composition through the enrichment of mucin-degrading A. muciniphila as well as several SCFA-producing microbiota. Future studies are needed to determine if these shifts mediate metformin’s glycemic and anti-inflammatory properties.

Diabetes and Hypertension: A Position Statement by the American Diabetes Association

Abstract: Hypertension is common among patients with diabetes, with the prevalence depending on type and duration of diabetes, age, sex, race/ethnicity, BMI, history of glycemic control, and the presence of kidney disease, among other factors (1–3). Furthermore, hypertension is a strong risk factor for atherosclerotic cardiovascular disease (ASCVD), heart failure, and microvascular complications. ASCVD—defined as acute coronary syndrome, myocardial infarction (MI), angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin—is the leading cause of morbidity and mortality for individuals with diabetes and is the largest contributor to the direct and indirect costs of diabetes. Numerous studies have shown that antihypertensive therapy reduces ASCVD events, heart failure, and microvascular complications in people with diabetes (4–8). Large benefits are seen when multiple risk factors are addressed simultaneously (9). There is evidence that ASCVD morbidity and mortality have decreased for people with diabetes since 1990 (10,11) likely due in large part to improvements in blood pressure control (12–14). This Position Statement is intended to update the assessment and treatment of hypertension among people with diabetes, including advances in care since the American Diabetes Association (ADA) last published a Position Statement on this topic in 2003 (3). #### Recommendations

Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial*

Abstract: OBJECTIVE To compare the efficacy and safety of once-weekly semaglutide 1.0 mg s.c. with exenatide extended release (ER) 2.0 mg s.c. in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS In this phase 3a, open-label, parallel-group, randomized controlled trial, 813 subjects with type 2 diabetes taking oral antidiabetic drugs were randomized (1:1) to semaglutide 1.0 mg or exenatide ER 2.0 mg for 56 weeks. The primary end point was change from baseline in HbA 1c at week 56. RESULTS Mean HbA 1c (8.3% [67.7 mmol/mol] at baseline) was reduced by 1.5% (16.8 mmol/mol) with semaglutide and 0.9% (10.0 mmol/mol) with exenatide ER (estimated treatment difference vs. exenatide ER [ETD] –0.62% [95% CI –0.80, –0.44] [–6.78 mmol/mol (95% CI –8.70, –4.86)]; P P 1c CONCLUSIONS Semaglutide 1.0 mg was superior to exenatide ER 2.0 mg in improving glycemic control and reducing body weight after 56 weeks of treatment; the drugs had comparable safety profiles. These results indicate that semaglutide treatment is highly effective for subjects with type 2 diabetes who are inadequately controlled on oral antidiabetic drugs.

The Fallacy of Average: How Using HbA 1c Alone to Assess Glycemic Control Can Be Misleading

Abstract: HbA1c is a valuable metric for comparing treatment groups in a randomized trial, for assessing glycemic trends in a population over time, or for cross-sectional comparisons of glycemic control in different populations. However, what is not widely appreciated is that HbA1c may not be a good indicator of an individual patient’s glycemic control because of the wide range of mean glucose concentrations and glucose profiles that can be associated with a given HbA1c level. To illustrate this point, we plotted mean glucose measured with continuous glucose monitoring (CGM) versus central laboratory–measured HbA1c in 387 participants in three randomized trials, showing that not infrequently HbA1c may underestimate or overestimate mean glucose, sometimes substantially. Thus, if HbA1c is to be used to assess glycemic control, it is imperative to know the patient’s actual mean glucose to understand how well HbA1c is an indicator of the patient’s glycemic control. With knowledge of the mean glucose, an estimated HbA1c (eA1C) can be calculated with the formula provided in this article to compare with the measured HbA1c. Estimating glycemic control from HbA1c alone is in essence applying a population average to an individual, which can be misleading. Thus, a patient’s CGM glucose profile has considerable value for optimizing his or her diabetes management. In this era of personalized, precision medicine, there are few better examples with respect to the fallacy of applying a population average to a specific patient rather than using specific information about the patient to determine the optimal approach to treatment.

Management of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Call to Action

Abstract: Traditionally a disease of hepatologists, nonalcoholic fatty liver disease (NAFLD) has recently become a major concern for a broad spectrum of health care providers. Endocrinologists and those caring for patients with type 2 diabetes mellitus (T2DM) are at center stage, as T2DM appears to worsen the course of NAFLD and the liver disease makes diabetes management more challenging. However, the nature of this relationship remains incompletely understood. Although the increasing prevalence of NAFLD is frequently attributed to the epidemic of obesity and is often oversimplified as the "hepatic manifestation of the metabolic syndrome," it is a much more complex disease process that may also be observed in nonobese individuals and in patients without clinical manifestations of the metabolic syndrome. It carries both metabolic and liver-specific complications that make its approach unique among medical conditions. Diabetes appears to promote the development of nonalcoholic steatohepatitis (NASH), the more severe form of the disease, and increases the risk of cirrhosis and hepatocellular carcinoma. Patients and physicians face many uncertainties, including fragmented information on the natural history of the disease, challenges in the diagnosis of NASH, and few pharmacological agents with proven efficacy. However, recent advances in diagnosis and treatment, combined with the risk of serious consequences from inaction, call for health care providers to be more proactive in the management of patients with T2DM and NASH.

Toward Defining the Threshold Between Low and High Glucose Variability in Diabetes

Abstract: OBJECTIVE To define the threshold for excess glucose variability (GV), one of the main features of dysglycemia in diabetes. RESEARCH DESIGN AND METHODS A total of 376 persons with diabetes investigated at the University Hospital of Montpellier (Montpellier, France) underwent continuous glucose monitoring. Participants with type 2 diabetes were divided into several groups—groups 1, 2a, 2b, and 3 ( n = 82, 28, 65, and 79, respectively)—according to treatment: 1 ) diet and/or insulin sensitizers alone; 2 ) oral therapy including an insulinotropic agent, dipeptidyl peptidase 4 inhibitors (group 2a) or sulfonylureas (group 2b); or 3 ) insulin. Group 4 included 122 persons with type 1 diabetes. Percentage coefficient of variation for glucose (%CV = [(SD of glucose)/(mean glucose)] × 100) and frequencies of hypoglycemia (interstitial glucose RESULTS Percentages of CV (median [interquartile range]; %) increased significantly ( P P P 36% were compared with those with %CV ≤36%. CONCLUSIONS A %CV of 36% appears to be a suitable threshold to distinguish between stable and unstable glycemia in diabetes because beyond this limit, the frequency of hypoglycemia is significantly increased, especially in insulin-treated subjects.

A National Effort to Prevent Type 2 Diabetes: Participant-Level Evaluation of CDC's National Diabetes Prevention Program.

Abstract: OBJECTIVE To assess participant-level results from the first 4 years of implementation of the National Diabetes Prevention Program (National DPP), a national effort to prevent type 2 diabetes in those at risk through structured lifestyle change programs. RESEARCH DESIGN AND METHODS Descriptive analysis was performed on data from 14,747 adults enrolled in year-long type 2 diabetes prevention programs during the period February 2012 through January 2016. Data on attendance, weight, and physical activity minutes were summarized and predictors of weight loss were examined using a mixed linear model. All analyses were performed using SAS 9.3. RESULTS Participants attended a median of 14 sessions over an average of 172 days in the program (median 134 days). Overall, 35.5% achieved the 5% weight loss goal (average weight loss 4.2%, median 3.1%). Participants reported a weekly average of 152 min of physical activity (median 128 min), with 41.8% meeting the physical activity goal of 150 min per week. For every additional session attended and every 30 min of activity reported, participants lost 0.3% of body weight ( P CONCLUSIONS During the first 4 years, the National DPP has achieved widespread implementation of the lifestyle change program to prevent type 2 diabetes, with promising early results. Greater duration and intensity of session attendance resulted in a higher percent of body weight loss overall and for subgroups. Focusing on retention may reduce disparities and improve overall program results. Further program expansion and investigation is needed to continue lowering the burden of type 2 diabetes nationally.

Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006-2013.

Abstract: OBJECTIVE To examine temporal trends in utilization of glucose-lowering medications, glycemic control, and rate of severe hypoglycemia among patients with type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS Using claims data from 1.66 million privately insured and Medicare Advantage patients with T2DM from 2006 to 2013, we estimated the annual 1 ) age- and sex-standardized proportion of patients who filled each class of agents; 2 ) age-, sex-, race-, and region-standardized proportion with hemoglobin A 1c (HbA 1c ) 3 ) age- and sex-standardized rate of severe hypoglycemia among those using medications. Proportions were calculated overall and stratified by age-group (18–44, 45–64, 65–74, and ≥75 years) and number of chronic comorbidities (zero, one, and two or more). RESULTS From 2006 to 2013, use increased for metformin (from 47.6 to 53.5%), dipeptidyl peptidase 4 inhibitors (0.5 to 14.9%), and insulin (17.1 to 23.0%) but declined for sulfonylureas (38.8 to 30.8%) and thiazolidinediones (28.5 to 5.6%; all P 1c P 1c ≥9% increased (9.9 to 12.2%; P P = 0.72), declined modestly among the oldest patients (from 2.9 to 2.3; P P = 0.36). CONCLUSIONS During the recent 8-year period, the use of glucose-lowering drugs has changed dramatically among patients with T2DM. Overall glycemic control has not improved and remains poor among nearly a quarter of the youngest patients. The overall rate of severe hypoglycemia remains largely unchanged.

Standardizing Clinically Meaningful Outcome Measures Beyond HbA 1c for Type 1 Diabetes: A Consensus Report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange.

Abstract: OBJECTIVE To identify and define clinically meaningful type 1 diabetes outcomes beyond hemoglobin A 1c (HbA 1c ) based upon a review of the evidence, consensus from clinical experts, and input from researchers, people with type 1 diabetes, and industry. Priority outcomes include hypoglycemia, hyperglycemia, time in range, diabetic ketoacidosis (DKA), and patient-reported outcomes (PROs). While priority outcomes for type 1 and type 2 diabetes may overlap, type 1 diabetes was the focus of this work. RESEARCH AND METHODS A Steering Committee—comprising representatives from the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange—was the decision-making body for the Type 1 Diabetes Outcomes Program. Their work was informed by input from researchers, industry, and people with diabetes through Advisory Committees representing each stakeholder group. Stakeholder surveys were used to identify priority outcomes. The outcomes prioritized in the surveys were hypoglycemia, hyperglycemia, time in range, DKA, and PROs. To develop consensus on the definitions of these outcomes, the Steering Committee relied on published evidence, their clinical expertise, and feedback from the Advisory Committees. RESULTS The Steering Committee developed definitions for hypoglycemia, hyperglycemia, time in range, and DKA in type 1 diabetes. The definitions reflect their assessment of the outcome’s short- and long-term clinical impact on people with type 1 diabetes. Knowledge gaps to be addressed by future research were identified. The Steering Committee discussed PROs and concluded that further type 1 diabetes–specific development is needed. CONCLUSIONS The Steering Committee recommends use of the defined clinically meaningful outcomes beyond HbA 1c in the research, development, and evaluation of type 1 diabetes therapies.

In Utero Exposure to Maternal Hyperglycemia Increases Childhood Cardiometabolic Risk in Offspring

Abstract: OBJECTIVE The objective of this study was to evaluate the effect of maternal hyperglycemia during pregnancy on cardiometabolic risk in offspring during early childhood. RESEARCH DESIGN AND METHODS A total of 970 mothers who had joined the Hyperglycemia and Adverse Pregnancy Outcome study were reevaluated, together with their child born during the study period, 7 years after delivery. RESULTS Offspring born to mothers diagnosed with gestational diabetes mellitus (GDM), as defined by the World Health Organization 2013 GDM criteria, had higher rates of abnormal glucose tolerance (4.7% vs. 1.7%; P = 0.04), higher rates of overweight or obesity, greater BMI, higher blood pressure (BP), lower oral disposition index, and a trend toward reduced β-cell function compared with those born to mothers without GDM. For each SD increase in maternal fasting, 1-h, and 2-h glucose levels on oral glucose tolerance tests (OGTTs) between 24 and 32 weeks of the index pregnancy, the risk of abnormal glucose tolerance in the offspring showed a corresponding increase (adjusted odds ratio [OR] 1.85–2.00). The associations were independent of BMI before pregnancy, childhood obesity, or being born large for gestational age. The area under the curve for glucose levels during the five-point OGTT increased to a similar extent in boys and girls with each SD increase in maternal 1-h and 2-h plasma glucose on OGTTs during pregnancy. All three maternal glucose levels were also associated with increased adjusted ORs for childhood overweight or obesity and adiposity among girls, but not boys. CONCLUSIONS Maternal hyperglycemia in pregnancy is independently associated with offsprings’ risk of abnormal glucose tolerance, obesity, and higher BP at 7 years of age. Its effect on childhood adiposity was apparent only in girls, not boys.

Effect of Saxagliptin on Renal Outcomes in the SAVOR-TIMI 53 Trial.

Abstract: OBJECTIVE Dipeptidyl peptidase 4 inhibitors may have a protective effect in diabetic nephropathy. RESEARCH DESIGN AND METHODS We studied renal outcomes of 16,492 patients with type 2 diabetes, randomized to saxagliptin versus placebo and followed for a median of 2.1 years in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial. RESULTS At baseline, 9,696 (58.8%) subjects had normoalbuminuria (albumin/creatinine ratio [ACR] 300 mg/g). Treatment with saxagliptin was associated with improvement in and/or less deterioration in ACR categories from baseline to end of trial (EOT) (P = 0.021, P 50 mL/min/body surface area per 1.73 m2 (BSA), −105 mg/g (P = 0.011) for 50 ≥ eGFR ≥ 30 mL/min/BSA, and −245.2 mg/g (P = 0.086) for eGFR 6.0 mg/dL, were similar as well. CONCLUSIONS Treatment with saxagliptin improved ACR, even in the normoalbuminuric range, without affecting eGFR. The beneficial effect of saxagliptin on albuminuria could not be explained by its effect on glycemic control.

REPLACE-BG: A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Well-Controlled Type 1 Diabetes

Abstract: OBJECTIVE To determine whether the use of continuous glucose monitoring (CGM) without confirmatory blood glucose monitoring (BGM) measurements is as safe and effective as using CGM adjunctive to BGM in adults with well-controlled type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS A randomized noninferiority clinical trial was conducted at 14 sites in the T1D Exchange Clinic Network. Participants were ≥18 years of age (mean 44 ± 14 years), had T1D for ≥1 year (mean duration 24 ± 12 years), used an insulin pump, and had an HbA1c ≤9.0% (≤75 mmol/mL) (mean 7.0 ± 0.7% [53 ± 7.7 mmol/mol]); prestudy, 47% were CGM users. Participants were randomly assigned 2:1 to the CGM-only (n = 149) or CGM+BGM (n = 77) group. The primary outcome was time in range (70–180 mg/dL) over the 26-week trial, with a prespecified noninferiority limit of 7.5%. RESULTS CGM use averaged 6.7 ± 0.5 and 6.8 ± 0.4 days/week in the CGM-only and CGM+BGM groups, respectively, over the 26-week trial. BGM tests per day (including the two required daily for CGM calibration) averaged 2.8 ± 0.9 and 5.4 ± 1.4 in the two groups, respectively (P CONCLUSIONS Use of CGM without regular use of confirmatory BGM is as safe and effective as using CGM with BGM in adults with well-controlled T1D at low risk for severe hypoglycemia.

Type 2 Diabetes in the Real World: The Elusive Nature of Glycemic Control

Abstract: Despite U.S. Food and Drug Administration (FDA) approval of over 40 new treatment options for type 2 diabetes since 2005, the latest data from the National Health and Nutrition Examination Survey show that the proportion of patients achieving glycated hemoglobin (HbA1c) <7.0% (<53 mmol/mol) remains around 50%, with a negligible decline between the periods 2003-2006 and 2011-2014. The Healthcare Effectiveness Data and Information Set reports even more alarming rates, with only about 40% and 30% of patients achieving HbA1c <7.0% (<53 mmol/mol) in the commercially insured (HMO) and Medicaid populations, respectively, again with virtually no change over the past decade. A recent retrospective cohort study using a large U.S. claims database explored why clinical outcomes are not keeping pace with the availability of new treatment options. The study found that HbA1c reductions fell far short of those reported in randomized clinical trials (RCTs), with poor medication adherence emerging as the key driver behind the disconnect. In this Perspective, we examine the implications of these findings in conjunction with other data to highlight the discrepancy between RCT findings and the real world, all pointing toward the underrealized promise of FDA-approved therapies and the critical importance of medication adherence. While poor medication adherence is not a new issue, it has yet to be effectively addressed in clinical practice-often, we suspect, because it goes unrecognized. To support the busy health care professional, innovative approaches are sorely needed.

Comparison of Ipragliflozin and Pioglitazone Effects on Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Randomized, 24-Week, Open-Label, Active-Controlled Trial

Abstract: OBJECTIVE To compare the efficacy of ipragliflozin versus pioglitazone in patients with type 2 diabetes complicated by nonalcoholic fatty liver disease (NAFLD). RESEARCH DESIGN AND METHODS In this open-label, randomized, active-controlled trial, we randomly assigned 66 patients with type 2 diabetes and NAFLD to receive ipragliflozin 50 mg ( n = 32) or pioglitazone 15–30 mg ( n = 34) orally once daily. The primary outcome was a change from baseline in the liver-to-spleen attenuation ratio (L/S ratio) on computed tomography at week 24. RESULTS At week 24, the mean ± SD L/S ratio had increased by 0.22 (from 0.80 ± 0.24 to 1.00 ± 0.18) in the ipragliflozin group and 0.21 (from 0.78 ± 0.26 to 0.98 ± 0.16) in the pioglitazone group ( P = 0.90). Serum aspartate and alanine aminotransferase levels, HbA 1c , and fasting plasma glucose were similarly reduced in the two treatment groups. Nevertheless, body weight and visceral fat area showed significant reductions only in the ipragliflozin group compared with the pioglitazone group ( P P = 0.0013, respectively). There were no serious adverse events in either group. CONCLUSIONS Compared with pioglitazone, ipragliflozin exerts equally beneficial effects on NAFLD and glycemic control during the treatment of patients with type 2 diabetes complicated by NAFLD. Furthermore, ipragliflozin significantly reduced body weight and abdominal fat area.

Prevalence of and Risk Factors for Diabetic Peripheral Neuropathy in Youth With Type 1 and Type 2 Diabetes: SEARCH for Diabetes in Youth Study.

Abstract: OBJECTIVE We assessed the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) enrolled in the SEARCH for Diabetes in Youth (SEARCH) study. RESEARCH DESIGN AND METHODS The Michigan Neuropathy Screening Instrument (MNSI) was used to assess DPN in 1,734 youth with T1D (mean ± SD age 18 ± 4 years, T1D duration 7.2 ± 1.2 years, and HbA1c 9.1 ± 1.9%) and 258 youth with T2D (age 22 ± 3.5 years, T2D duration 7.9 ± 2 years, and HbA1c 9.4 ± 2.3%) who were enrolled in the SEARCH study and had ≥5 years of diabetes duration. DPN was defined as an MNSI exam score of >2. Glycemic control over time was estimated as area under the curve for HbA1c. RESULTS The prevalence of DPN was 7% in youth with T1D and 22% in youth with T2D. Risk factors for DPN in youth with T1D were older age, longer diabetes duration, smoking, increased diastolic blood pressure, obesity, increased LDL cholesterol and triglycerides, and lower HDL cholesterol (HDL-c). In youth with T2D, risk factors were older age, male sex, longer diabetes duration, smoking, and lower HDL-c. Glycemic control over time was worse among those with DPN compared with those without for youth with T1D (odds ratio 1.53 [95% CI 1.24; 1.88]) but not for youth with T2D (1.05 [0.7; 1.56]). CONCLUSIONS The high rates of DPN among youth with diabetes are a cause of concern and suggest a need for early screening and better risk factor management. Interventions in youth that address poor glycemic control and dyslipidemia may prevent or delay debilitating neuropathic complications.

The Impact of Continuous Glucose Monitoring on Markers of Quality of Life in Adults With Type 1 Diabetes: Further Findings From the DIAMOND Randomized Clinical Trial.

Abstract: OBJECTIVE Continuous glucose monitoring (CGM) improves glycemic control, but data are inconclusive about its influence on quality of life (QOL). We investigated the impact of 24 weeks of CGM use on QOL in adults with type 1 diabetes (T1D) who use multiple daily insulin injections. RESEARCH DESIGN AND METHODS DIAMOND (Multiple Daily Injections and Continuous Glucose Monitoring in Diabetes) was a prospective randomized trial that assessed CGM versus self-monitoring of blood glucose (SMBG) only in 158 adults with poorly controlled T1D. At baseline and study end, participants completed QOL measures that assessed overall well-being (WHO-5), health status (EQ-5D-5L), diabetes distress (DDS), hypoglycemic fear (worry subscale of the HFS-II), and hypoglycemic confidence (HCS). At study end, CGM participants completed the CGM Satisfaction Survey. Linear regression analyses compared treatment group changes in QOL outcomes over time. Associations between CGM satisfaction and change in QOL outcomes and in glycemic control indices were assessed. RESULTS The CGM group demonstrated a greater increase in hypoglycemic confidence ( P = 0.01) and a greater decrease in diabetes distress ( P = 0.01) than the SMBG group. No significant group differences in well-being, health status, or hypoglycemic fear were observed. CGM satisfaction was not significantly associated with glycemic changes but was associated with reductions in diabetes distress ( P P = 0.02) and increases in hypoglycemic confidence ( P P = 0.01). CONCLUSIONS CGM contributes to significant improvement in diabetes-specific QOL (i.e., diabetes distress, hypoglycemic confidence) in adults with T1D, but not with QOL measures not specific to diabetes (i.e., well-being, health status). CGM satisfaction was associated with most of the QOL outcomes but not with glycemic outcomes.

Diabetes Device Use in Adults With Type 1 Diabetes: Barriers to Uptake and Potential Intervention Targets.

Abstract: OBJECTIVE Diabetes devices (insulin pumps, continuous glucose monitors [CGMs]) are associated with benefits for glycemic control, yet uptake of these devices continues to be low. Some barriers to device uptake may be modifiable through psychosocial intervention, but little is known about which barriers and which patients to target. RESEARCH DESIGN AND METHODS We surveyed 1,503 adult T1D Exchange participants (mean age 35.3 [SD 14.8] years, diagnosis duration 20.4 [SD 12.5] years) to investigate barriers to device uptake, understand profiles of device users versus nonusers, and explore differences by age and sex. Scales used were the Diabetes Distress Scale, technology use attitudes (general and diabetes-specific), and barriers to device use and reasons for discontinuing devices. RESULTS Most commonly endorsed modifiable barriers were related to the hassle of wearing devices (47%) and disliking devices on one’s body (35%). CGM users (37%) were older than nonusers (mean 38.3 vs. 33.5 years), had diabetes for longer (22.9 vs. 18.8 years), had more positive technology attitudes than older age-groups (22.6–26.0 vs. 21.4–24.8), and reported fewer barriers to using diabetes technology than nonusers (3.3 vs. 4.3). The youngest age-group (18–25 years) had the lowest CGM (26% vs. 40–48%) and insulin pump (64% vs. 69–77%) uptake, highest diabetes distress (2.2 vs. 1.8–2.1), and highest A1C levels (8.3% [67 mmol/mol] vs. 7.2–7.4% [55–57 mmol/mol]). CONCLUSIONS Efforts to increase device use need to target physical barriers to wearing devices. Because young adults had the lowest device uptake rates, highest distress, and highest A1C compared with older age-groups, they should be the focus of future interventions to increase device use.

Triglyceride and HDL-C Dyslipidemia and Risks of Coronary Heart Disease and Ischemic Stroke by Glycemic Dysregulation Status: The Strong Heart Study.

Abstract: OBJECTIVE High triglyceride (TG) levels and low HDL cholesterol (HDL-C) levels are risk factors for cardiovascular disease. It is unclear whether this relationship depends on glycemic dysregulation, sex, or LDL cholesterol (LDL-C) level. RESEARCH DESIGN AND METHODS We studied 3,216 participants (40% men, 41% with diabetes) who were free of cardiovascular disease at baseline in a community-based, prospective cohort of American Indians (median follow-up 17.7 years). Cox models estimated hazard ratios (HRs) and 95% CIs for incident ischemic stroke and coronary heart disease (CHD) in relation to combined TG and HDL-C status, where a fasting TG level ≥150 mg/dL was “high” and a fasting HDL-C level RESULTS Participants with high TG and low HDL levels had a 1.32-fold greater HR (95% CI 1.06–1.64) for CHD than those with normal TG and normal HDL levels. It was observed in participants with diabetes, but not in those without diabetes, that high TG plus low HDL levels were associated with a 1.54-fold greater HR (95% CI 1.15–2.06) for CHD (P value for interaction = 0.003) and a 2.13-fold greater HR (95% CI 1.06–4.29) for stroke (P value for interaction = 0.060). High TG and low HDL level was associated with CHD risk in participants with an LDL-C level of ≥130 mg/dL, but this was not observed in those participants with lower LDL-C levels. Sex did not appear to modify these associations. CONCLUSIONS Adults with both high TG and low HDL-C, particularly those with diabetes, have increased risks of incident CHD and stroke. In particular, those with an LDL-C level ≥130 mg/dL may have an increased risk of incident stroke.

2017 National Standards for Diabetes Self-Management Education and Support

Abstract: By the most recent estimates, 30.3 million people in the U.S. have diabetes. An estimated 23.1 million have been diagnosed with diabetes and 7.2 million are believed to be living with undiagnosed diabetes. At the same time, 84.1 million people are at increased risk for type 2 diabetes. Thus, more than 114 million Americans are at risk for developing the devastating complications of diabetes (1). Diabetes self-management education and support (DSMES) is a critical element of care for all people with diabetes. DSMES is the ongoing process of facilitating the knowledge, skills, and ability necessary for diabetes self-care, as well as activities that assist a person in implementing and sustaining the behaviors needed to manage his or her condition on an ongoing basis, beyond or outside of formal self-management training. In previous National Standards for Diabetes Self-Management Education and Support (Standards), DSMS and DSME were defined separately, but these Standards aim to reflect the value of ongoing support and multiple services. The Standards define timely, evidence-based, quality DSMES services that meet or exceed the Medicare diabetes self-management training (DSMT) regulations, however, these Standards do not guarantee reimbursement. These Standards provide evidence for all diabetes self-management education providers including those that do not plan to seek reimbursement for DSMES. The current Standards’ evidence clearly identifies the need to provide person-centered services that embrace the ever-increasing technological engagement platforms and systems. The hope is that payers will view these Standards as a tool for reviewing DSMES reimbursement requirements and consider change to align with the way their beneficiaries’ engagement preferences have evolved. Research confirms that less than 5% of Medicare beneficiaries utilize their DSMES benefits (2,3). Changes in reimbursement policies stand to increase DSMES access and utilization, which will result in positive impact to beneficiaries’ clinical outcomes, quality of …

Incidence, Demographics, and Clinical Characteristics of Diabetes of the Exocrine Pancreas (Type 3c): A Retrospective Cohort Study

Abstract: OBJECTIVE This study was conducted to describe the incidence of diabetes following pancreatic disease, assess how these patients are classified by clinicians, and compare clinical characteristics with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS Primary care records in England ( n = 2,360,631) were searched for incident cases of adult-onset diabetes between 1 January 2005 and 31 March 2016. We examined demographics, diabetes classification, glycemic control, and insulin use in those with and without pancreatic disease (subcategorized into acute pancreatitis or chronic pancreatic disease) before diabetes diagnosis. Regression analysis was used to control for baseline potential risk factors for poor glycemic control (HbA 1c ≥7% [53 mmol/mol]) and insulin requirement. RESULTS We identified 31,789 new diagnoses of adult-onset diabetes. Diabetes following pancreatic disease (2.59 [95% CI 2.38–2.81] per 100,000 person-years) was more common than type 1 diabetes (1.64 [1.47–1.82]; P 2 . Diabetes following pancreatic disease was associated with poor glycemic control (adjusted odds ratio, 1.7 [1.3–2.2]; P CONCLUSIONS Diabetes of the exocrine pancreas is frequently labeled type 2 diabetes but has worse glycemic control and a markedly greater requirement for insulin.

Cognitive Dysfunction in Older Adults With Diabetes: What a Clinician Needs to Know

Abstract: One of the challenges of managing older adults with diabetes is the individualization of care in people with multiple comorbid conditions. Although macrovascular and microvascular complications of diabetes are well recognized, there is a lack of awareness regarding other conditions such as cognitive dysfunction, depression, and physical disabilities. Cognitive dysfunction is of particular importance because of its impact on self-care and quality of life. In this Perspective, I discuss common and practical questions faced by clinicians managing diabetes in older adults who also have cognitive dysfunction.

Sulfonylureas and the Risks of Cardiovascular Events and Death: A Methodological Meta-Regression Analysis of the Observational Studies.

Abstract: Recent randomized trials have compared the newer antidiabetic agents to treatments involving sulfonylureas, drugs associated with increased cardiovascular risks and mortality in some observational studies with conflicting results. We reviewed the methodology of these observational studies by searching MEDLINE from inception to December 2015 for all studies of the association between sulfonylureas and cardiovascular events or mortality. Each study was appraised with respect to the comparator, the outcome, and study design-related sources of bias. A meta-regression analysis was used to evaluate heterogeneity. A total of 19 studies were identified, of which six had no major design-related biases. Sulfonylureas were associated with an increased risk of cardiovascular events and mortality in five of these studies (relative risks 1.16-1.55). Overall, the 19 studies resulted in 36 relative risks as some studies assessed multiple outcomes or comparators. Of the 36 analyses, metformin was the comparator in 27 (75%) and death was the outcome in 24 (67%). The relative risk was higher by 13% when the comparator was metformin, by 20% when death was the outcome, and by 7% when the studies had design-related biases. The lowest predicted relative risk was for studies with no major bias, comparator other than metformin, and cardiovascular outcome (1.06 [95% CI 0.92-1.23]), whereas the highest was for studies with bias, metformin comparator, and mortality outcome (1.53 [95% CI 1.43-1.65]). In summary, sulfonylureas were associated with an increased risk of cardiovascular events and mortality in the majority of studies with no major design-related biases. Among studies with important biases, the association varied significantly with respect to the comparator, the outcome, and the type of bias. With the introduction of new antidiabetic drugs, the use of appropriate design and analytical tools will provide their more accurate cardiovascular safety assessment in the real-world setting.

Genetic and Environmental Interactions Modify the Risk of Diabetes-Related Autoimmunity by 6 Years of Age: The TEDDY Study

Abstract: OBJECTIVE We tested the associations between genetic background and selected environmental exposures with respect to islet autoantibodies and type 1 diabetes. RESEARCH DESIGN AND METHODS Infants with HLA-DR high-risk genotypes were prospectively followed for diabetes-related autoantibodies. Single nucleotide polymorphisms (SNPs) came from the Illumina ImmunoChip and environmental exposure data were by parental report. Children were followed to age 6 years. RESULTS Insulin autoantibodies occurred earlier than GAD antibody (GADA) and then declined, while GADA incidence rose and remained constant (significant in HLA-DR4 but not in the DR3/3 children). The presence of SNPs rs2476601 ( PTPN22 ) and rs2292239 ( ERBB3 ) demonstrated increased risk of both autoantibodies to insulin (IAA) only and GADA only. SNP rs689 ( INS ) was protective of IAA only, but not of GADA only. The rs3757247 ( BACH2 ) SNP demonstrated increased risk of GADA only. Male sex, father or sibling as the diabetic proband, introduction of probiotics under 28 days of age, and weight at age 12 months were associated with IAA only, but only father as the diabetic proband and weight at age 12 months were associated with GADA only. Mother as the diabetic proband was not a significant risk factor. CONCLUSIONS These results show clear differences in the initiation of autoimmunity according to genetic factors and environmental exposures that give rise to IAA or GADA as the first appearing indication of autoimmunity.

Accuracy and Longevity of an Implantable Continuous Glucose Sensor in the PRECISE Study: A 180-Day, Prospective, Multicenter, Pivotal Trial

Abstract: OBJECTIVE It is known that continuous glucose monitoring (CGM) systems can lower mean glucose compared with episodic self-monitoring of blood glucose. Implantable CGM systems may provide additional benefits. RESEARCH DESIGN AND METHODS We studied the Eversense (Senseonics Inc.) implantable CGM sensor in 71 participants aged 18 years and older with type 1 and type 2 diabetes in a 180-day multinational, multicenter pivotal trial. Participants used the CGM system at home and in the clinic. CGM accuracy was assessed during eight in-clinic visits with the mean absolute relative difference (MARD) for venous reference glucose values >4.2 mmol/L as the primary end point. Secondary end points included Clarke Error Grid Analysis and alarm performance. The primary safety outcome was device-related serious adverse events. This trial is registered with ClinicalTrials.gov, number NCT02154126. RESULTS The MARD value against reference glucose values >4.2 mmol/L was 11.1% (95% CI 10.5, 11.7). Clarke Error Grid Analysis showed 99.2% of samples in the clinically acceptable error zones A and B. Eighty-one percent of hypoglycemic events were detected by the CGM system within 30 min. No device-related serious adverse events occurred during the study. CONCLUSIONS Our results indicate the safety and accuracy of this new type of implantable CGM system and support it as an alternative for transcutaneous CGM.

Diabetes and Aging: Unique Considerations and Goals of Care

Abstract: Diabetes in older adults is a growing public health burden. The unprecedented aging of the world's population is a major contributor to the diabetes epidemic, and older adults represent one of the fastest growing segments of the diabetes population. Of impending concern is that these numbers are projected to grow dramatically over the next few decades (1,2). Almost one-third of U.S. adults over the age of 65 years have diabetes. Approximately half of those are undiagnosed, and an additional one-third of older adults have prediabetes (3). Persons with diabetes today are living much longer compared with those in the past. We also recognize that management of older adults with diabetes is clearly more complicated given the observation that they commonly have multiple coexisting medical conditions that can impact clinical management. While rates of diabetes-related complications have declined overall in the general population, the incidence rates of macrovascular complications such as acute myocardial infarction and stroke continue to be the highest in older age-groups. These individuals also have the highest rate of diabetes-related end-stage renal disease (4). Heterogeneity in the health status of older adults (ranging from robust and otherwise healthy individuals to those with frailty and multiple comorbid conditions) and the paucity of evidence from clinical trials represent a challenge to making generalized treatment recommendations for older adults. Although many more individuals with type 1 diabetes are living longer (5), type 2 diabetes remains the most common type in older age-groups. Furthermore, older adults with diabetes may either have elderly onset disease (diagnosed at age 65 years or older) or long-standing diabetes with onset in middle age or earlier years (6), adding to the complexity of managing diabetes in older adults. Consequently, the American Diabetes Association (ADA) organized a Consensus Development Conference on Diabetes and Older Adults …

Fast-Acting Insulin Aspart Improves Glycemic Control in Basal-Bolus Treatment for Type 1 Diabetes: Results of a 26-Week Multicenter, Active-Controlled, Treat-to-Target, Randomized, Parallel-Group Trial (onset 1).

Abstract: OBJECTIVE This multicenter, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (faster aspart) versus conventional insulin aspart (IAsp) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS The primary end point was change from baseline in HbA1c after 26 weeks. After an 8-week run-in, subjects were randomized (1:1:1) to double-blind mealtime faster aspart (n = 381), IAsp (n = 380), or open-label postmeal faster aspart (n = 382)—each with insulin detemir. RESULTS HbA1c was reduced in both treatment groups, and noninferiority to IAsp was confirmed for both mealtime and postmeal faster aspart (estimated treatment difference [ETD] faster aspart–IAsp, mealtime, –0.15% [95% CI –0.23; –0.07], and postmeal, 0.04% [–0.04; 0.12]); mealtime faster aspart statistically significantly reduced HbA1c versus IAsp (P = 0.0003). Postprandial plasma glucose (PPG) increments were statistically significantly lower with mealtime faster aspart at 1 h (ETD –1.18 mmol/L [95% CI –1.65; –0.71], –21.21 mg/dL [–29.65; –12.77]; P CONCLUSIONS Faster aspart effectively improved HbA1c, and noninferiority to IAsp was confirmed, with superior PPG control for mealtime faster aspart versus IAsp. Subjects randomized to postmeal faster aspart for all meals maintained HbA1c noninferior to that obtained with mealtime IAsp.