Distinct protein kinase C isoforms drive the cell cycle re-entry of two separate populations of neonatal rat ventricular cardiomyocytes.

The present study tested the hypothesis that protein kinase C-α (PKC-α) recruitment in the presence of the p38α/ß MAPK inhibitor SB203580 facilitated the appearance and cell cycle re-entry of nestin(+)-neonatal rat ventricular cardiomyocytes (NNVMs) and induced a transcript profile delineating a proliferative phenotype. Phorbol 12,13-dibutyrate (PDBu) treatment did not induce de novo nestin expression or increase the cell cycle re-entry of 1-day-old NNVMs but significantly increased runt-related transcription factor 1 (Runx1) and p16 cell cycle inhibitor (CDKN2a) mRNA levels and downregulated epithelial cell transforming 2 (ECT2) mRNA expression. SB203580 administration to PDBu-treated NNVMs induced de novo nestin expression, preferentially increased the density (normalized to 500 NNVMs) of nestin(+)-NNVMs that incorporated 5-bromo-2'-deoxyuridine (PDBu, 1.4 ± 3 vs. PDBu/SB203580, 128 ± 34; n = 5 independent litters), significantly inhibited CDKN2a and Runx1 mRNA upregulation and reversed ECT2 mRNA downregulation. PDBu treatment of NNVMs reduced PKC-α, protein kinase-δ (PKC-δ) and protein kinase-ε (PKC-ε) protein levels and GF109203X (conventional PKC isoform inhibitor) selectively attenuated PKC-α protein downregulation. GF109203X administration to PDBu/SB203580-treated NNVMs significantly reduced the density of nestin(+)-NNVMs that incorporated 5-bromo-2'-deoxyuridine (PDBu/SB203580/GF109203X, 40 ± 46; n = 5). Moreover, GF109203X/PDBu/SB203580 treatment unmasked the predominant appearance of a separate NNVM population that incorporated 5-bromo-2'-deoxyuridine (PDBu/SB203580/GF109203X, 192 ± 42; n = 5) delineated by the absence of de novo nestin expression. Sotrastaurin (conventional/novel PKC isoform inhibitor) administration to PDBu/SB203580-treated NNVMs significantly attenuated the density of nestin(+)-NNVMs (PDBu/SB203580/sotrastaurin, 8 ± 10; n = 4) and nestin(-)-NNVMs (PDBu/SB203580/sotrastaurin, 64 ± 30; n = 4) that incorporated 5-bromo-2'-deoxyuridine. These data reveal that the neonatal rat heart contains at least two separate populations of NNVMs that re-enter the cell cycle and the preferential appearance of nestin(+)- or nestin(-)-NNVMs is driven by distinct PKC isoforms in the presence of SB203580.NEW & NOTEWORTHY The appearance of nestin(+)-neonatal rat ventricular cardiomyocytes that re-entered the cell cycle following phorbol ester stimulation in the presence of p38α/ß MAPK inhibitor SB203580 was associated with the inhibition of Runx1 and CDKN2a mRNA upregulation. PKC-α selectively induced the cell cycle re-entry of nestin(+)-neonatal rat ventricular cardiomyocytes. Pharmacological inhibition of PKC-α with concomitant p38α/ß MAPK suppression unmasked the cell cycle re-entry of a second population of neonatal rat ventricular cardiomyocytes in the absence of nestin expression.

Glucagon - the new 'insulin' in the pathophysiology of diabetes.

PURPOSE OF REVIEW: Autoimmune destruction of the ß cells is considered the key abnormality in type 1 diabetes mellitus and insulin replacement the primary therapeutic strategy. However, a lack of insulin is accompanied by disturbances in glucagon release, which is excessive postprandially, but insufficient during hypoglycaemia. In addition, replacing insulin alone appears insufficient for adequate glucose control. This review focuses on the growing body of evidence that glucagon abnormalities contribute significantly to the pathophysiology of diabetes and on recent efforts to target the glucagon axis as adjunctive therapy to insulin replacement. RECENT FINDINGS: This review discusses recent (since 2013) advances in abnormalities of glucagon regulation and their link to the pathophysiology of diabetes; new mechanisms of glucagon action and regulation; manipulation of glucagon in diabetes treatment; and analytical and systems biology tools to study glucagon regulation. SUMMARY: Recent efforts 'resurrected' glucagon as a key hormone in the pathophysiology of diabetes. New studies target its abnormal regulation and action that is key for improving diabetes treatment. The progress is promising, but major questions remain, including unravelling the mechanism of loss of glucagon counterregulation in type 1 diabetes mellitus and how best to manipulate glucagon to achieve more efficient and safer glycaemic control.

Impact of behavioral interventions in the management of adults with type 2 diabetes mellitus.

Research on the role of behavior change as an efficacious intervention for adults with type 2 diabetes is evolving. Searching PubMed and Ovid Medline, we identified and reviewed primarily randomized controlled trials from 2010 to 2013 of adults managing type 2 diabetes without insulin. All studies are evaluated in terms of the rigor of their design and their impact on glycosylated hemoglobin. The most efficacious interventions appear to be low-carbohydrate/glycemic load diets, combined aerobic and resistance training, and self-monitoring of blood glucose, which educates patients about the impact of their food selections and physical activity on their blood glucose.

Regional and racial disparities in major amputation rates among medicare beneficiaries with diabetes: a retrospective study in the southeastern USA.

Objective: While rates for non-traumatic lower extremity amputations (LEA) have been declining, concerns exist over disparities. Our objectives are to track major LEA (MLEA) rates over time among Medicare beneficiaries residing in a high diabetes prevalence region in the southeastern USA (the diabetes belt) and surrounding areas. Methods: We used Medicare claims files for ~900 000 fee-for-service beneficiaries aged ≥65 years in 2006-2015 to track MLEA rates per 1000 patients with diabetes. We additionally conducted a cross-sectional analysis of data for 2015 to compare regional and racial disparities in major amputation risks after adjusting for demographic, socioeconomic, access-to-care and foot complications and other health factors. The Centers for Disease Control and Prevention defined the diabetes belt as 644 counties across Appalachian and southeastern US counties with high prevalence. Results: MLEA rates were 3.9 per 1000 in the Belt compared with 2.8 in the surrounding counties in 2006 and decreased to 2.3 and 1.6 in 2015. Non-Hispanic black patients had 8.5 and 6.9 MLEAs per 1000 in 2006 and 4.8 and 3.5 in 2015 in the Belt and surrounding counties, respectively, while the rates were similar for non-Hispanic white patients in the two areas. Although amputation rates declined rapidly in both areas, non-Hispanic black patients in the Belt consistently had >3 times higher rates than non-Hispanic whites in the Belt. After adjusting for patient demographics, foot complications and healthcare access, non-Hispanic blacks in the Belt had about twice higher odds of MLEAs compared with non-Hispanic whites in the surrounding areas. Discussion: Our data show persistent disparities in major amputation rates between the diabetes belt and surrounding counties. Racial disparities were much larger in the Belt. Targeted policies to prevent MLEAs among non-Hispanic black patients are needed to reduce persistent disparities in the Belt.

Management of Individuals With Diabetes at High Risk for Hypoglycemia: An Endocrine Society Clinical Practice Guideline.

CONTEXT: Hypoglycemia in people with diabetes is common, especially in those taking medications such as insulin and sulfonylureas (SU) that place them at higher risk. Hypoglycemia is associated with distress in those with diabetes and their families, medication nonadherence, and disruption of life and work, and it leads to costly emergency department visits and hospitalizations, morbidity, and mortality. OBJECTIVE: To review and update the diabetes-specific parts of the 2009 Evaluation and Management of Adult Hypoglycemic Disorders: Endocrine Society Clinical Practice Guideline and to address developing issues surrounding hypoglycemia in both adults and children living with diabetes. The overriding objectives are to reduce and prevent hypoglycemia. METHODS: A multidisciplinary panel of clinician experts, together with a patient representative, and methodologists with expertise in evidence synthesis and guideline development, identified and prioritized 10 clinical questions related to hypoglycemia in people living with diabetes. Systematic reviews were conducted to address all the questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. RESULTS: The panel agreed on 10 questions specific to hypoglycemia risk and prevention in people with diabetes for which 10 recommendations were made. The guideline includes conditional recommendations for use of real-time continuous glucose monitoring (CGM) and algorithm-driven insulin pumps in people with type 1 diabetes (T1D), use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia, use of long-acting and rapid-acting insulin analogs, and initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia. Strong recommendations were made for structured diabetes education programs for those at high risk for hypoglycemia, use of glucagon preparations that do not require reconstitution vs those that do for managing severe outpatient hypoglycemia for adults and children, use of real-time CGM for individuals with T1D receiving multiple daily injections, and the use of inpatient glycemic management programs leveraging electronic health record data to reduce the risk of hypoglycemia. CONCLUSION: The recommendations are based on the consideration of critical outcomes as well as implementation factors such as feasibility and values and preferences of people with diabetes. These recommendations can be used to inform clinical practice and health care system improvement for this important complication for people living with diabetes.

A Systematic Review Supporting the Endocrine Society Guidelines: Management of Diabetes and High Risk of Hypoglycemia.

CONTEXT: Interventions targeting hypoglycemia in people with diabetes are important for improving quality of life and reducing morbidity and mortality. OBJECTIVE: To support development of the Endocrine Society Clinical Practice Guideline for management of individuals with diabetes at high risk for hypoglycemia. METHODS: We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence. RESULTS: We included 149 studies reporting on 43 344 patients. Continuous glucose monitoring (CGM) reduced episodes of severe hypoglycemia in patients with type 1 diabetes (T1D) and reduced the proportion of patients with hypoglycemia (blood glucose [BG] levels <54 mg/dL). There were no data on use of real-time CGM with algorithm-driven insulin pumps vs multiple daily injections with BG testing in people with T1D. CGM in outpatients with type 2 diabetes taking insulin and/or sulfonylureas reduced time spent with BG levels under 70 mg/dL. Initiation of CGM in hospitalized patients at high risk for hypoglycemia reduced episodes of hypoglycemia with BG levels lower than 54 mg/dL and time spent under 54 mg/dL. The proportion of patients with hypoglycemia with BG levels lower than 70 mg/dL and lower than 54 mg/dL detected by CGM was significantly higher than point-of-care BG testing. We found no data evaluating continuation of personal CGM in the hospital. Use of an inpatient computerized glycemic management program utilizing electronic health record data was associated with fewer patients with and episodes of hypoglycemia with BG levels lower than 70 mg/dL and fewer patients with severe hypoglycemia compared with standard care. Long-acting basal insulin analogs were associated with less hypoglycemia. Rapid-acting insulin analogs were associated with reduced severe hypoglycemia, though there were more patients with mild to moderate hypoglycemia. Structured diabetes education programs reduced episodes of severe hypoglycemia and time below 54 mg/dL in outpatients taking insulin. Glucagon formulations not requiring reconstitution were associated with longer times to recovery from hypoglycemia, although the proportion of patients who recovered completely from hypoglycemia was not different between the 2 groups. CONCLUSION: This systematic review summarized the best available evidence about several interventions addressing hypoglycemia in people with diabetes. This evidence base will facilitate development of clinical practice guidelines by the Endocrine Society.

Resolving the conundrum of islet transplantation by linking metabolic dysregulation, inflammation, and immune regulation.

Although type 1 diabetes cannot be prevented or reversed, replacement of insulin production by transplantation of the pancreas or pancreatic islets represents a definitive solution. At present, transplantation can restore euglycemia, but this restoration is short-lived, requires islets from multiple donors, and necessitates lifelong immunosuppression. An emerging paradigm in transplantation and autoimmunity indicates that systemic inflammation contributes to tissue injury while disrupting immune tolerance. We identify multiple barriers to successful islet transplantation, each of which either contributes to the inflammatory state or is augmented by it. To optimize islet transplantation for diabetes reversal, we suggest that targeting these interacting barriers and the accompanying inflammation may represent an improved approach to achieve successful clinical islet transplantation by enhancing islet survival, regeneration or neogenesis potential, and tolerance induction. Overall, we consider the proinflammatory effects of important technical, immunological, and metabolic barriers including: 1) islet isolation and transplantation, including selection of implantation site; 2) recurrent autoimmunity, alloimmune rejection, and unique features of the autoimmune-prone immune system; and 3) the deranged metabolism of the islet transplant recipient. Consideration of these themes reveals that each is interrelated to and exacerbated by the other and that this connection is mediated by a systemic inflammatory state. This inflammatory state may form the central barrier to successful islet transplantation. Overall, there remains substantial promise in islet transplantation with several avenues of ongoing promising research. This review focuses on interactions between the technical, immunological, and metabolic barriers that must be overcome to optimize the success of this important therapeutic approach.

An Innovative, Paradigm-Shifting Lifestyle Intervention to Reduce Glucose Excursions With the Use of Continuous Glucose Monitoring to Educate, Motivate, and Activate Adults With Newly Diagnosed Type 2 Diabetes: Pilot Feasibility Study.

BACKGROUND: Type 2 diabetes (T2D) is a growing epidemic in the United States, and metabolic control has not been improved over the last 10 years. Glycemic excursion minimization (GEM) is an alternative lifestyle treatment option focused on reducing postnutrient glucose excursions rather than reducing weight. GEM has been proven to be superior to routine care when delivered face to face, and equivalent or superior to conventional weight loss therapy, but it has not been evaluated among patients newly diagnosed with T2D or in a self-administered format. OBJECTIVE: This pilot study evaluated the feasibility of a self-administered version of GEM, augmented with continuous glucose monitoring (CGM), to improve metabolic control (hemoglobin A1c [HbA1c]) while diminishing or delaying the need for diabetes medications in adults recently diagnosed with T2D. These primary objectives were hypothesized to be achieved by reducing carbohydrate intake and increasing physical activity to diminish CGM glucose excursions, leading to the secondary benefits of an increase in diabetes empowerment and reduced diabetes distress, depressive symptoms, and BMI. METHODS: GEM was self-administered by 17 adults recently diagnosed with T2D (mean age 52 years, SD 11.6 years; mean T2D duration 3.9 months, SD 2.5 months; mean HbA1c levels 8.0%, SD 1.6%; 40% female; 33.3% non-White), with the aid of a 4-chapter pocket guide and diary, automated motivational text messaging, and feedback from an activity monitor, along with CGM and supplies for the 6-week intervention and the 3-month follow-up. Treatment was initiated with one telephone call reviewing the use of the technology and 3 days later with a second call reviewing the use of the GEM pocket guide and intervention. RESULTS: At 3-month follow-up, 67% of the participants' diabetes was in remission (HbA1c levels <6.5%), and only one participant started taking diabetes medication. Participants demonstrated a significant reduction in HbA1c levels (-1.8%; P<.001). Participants also experienced significant reductions in high-glycemic-load carbohydrates routinely consumed, CGM readings that were >140 mg/dL, diabetes distress, depressive symptoms, and BMI. Participants felt that use of the CGM was the most significant single element of the intervention. CONCLUSIONS: GEM augmented with CGM feedback may be an effective initial intervention for adults newly diagnosed with T2D. A self-administered version of GEM may provide primary care physicians and patients with a new tool to help people recently diagnosed with T2D achieve remission independent of medication and without weight loss as the primary focus. Future research is needed with a larger and more diverse sample.

Annual wellness visits are associated with increased use of preventive services in patients with diabetes living in the Diabetes Belt.

Objective: To examine whether Annual Wellness Visits (AWVs) were associated with increased use of preventive services in Medicare patients with diabetes living in the Diabetes Belt. Methods: We used a case-control design where outcomes were utilization of preventive services recommended for patients with diabetes (foot exam, eye exam, A1c test, and microalbuminuria test) and the exposure was AWVs using data for Medicare patients with diabetes in 2014 - 2015 residing in the Diabetes Belt (N = 412,009). Results: Only 13.4% of patients in 2014 and 17.4% in 2015 used AWVs. Eye exams (61% vs 53%), foot exams (93% vs 79%), A1c tests (81% vs 71%), and microalbuminuria tests (45% vs 28%) were more common among patients who had an AWV in the preceding year compared with those who did not. These differences remained significant after adjusting for patient demographics, comorbidities, county level medical resources, and geographic factors. Conclusions: AWVs were significantly associated with increased preventive care use among patients with diabetes living in the Diabetes Belt. Low AWV utilization by patients with diabetes in and around the Diabetes Belt is concerning.

Enhancing the Trustworthiness of the Endocrine Society's Clinical Practice Guidelines.

In an effort to enhance the trustworthiness of its clinical practice guidelines, the Endocrine Society has recently adopted new policies and more rigorous methodologies for its guideline program. In this Clinical Practice Guideline Communication, we describe these recent enhancements-many of which reflect greater adherence to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to guideline development-in addition to the rationale for such changes. Improvements to the Society's guideline development practices include, but are not limited to, enhanced inclusion of nonendocrinologist experts, including patient representatives, on guideline development panels; implementation of a more rigorous conflict/duality of interest policy; a requirement that all formal recommendations must be demonstrably underpinned by systematic evidence review; the explicit use of GRADE Evidence-to-Decision frameworks; greater use and explanation of standardized guideline language; and a more intentional approach to guideline updating. Lastly, we describe some of the experiential differences our guideline readers are most likely to notice.

Long-term follow-up of a randomized clinical trial comparing glycemic excursion minimization (GEM) to weight loss (WL) in the management of type 2 diabetes.

INTRODUCTION: We previously reported the physical, psychological and behavioral 3-month post-treatment results of a randomized controlled trial comparing glycemic excursion minimization (GEM) versus conventional weight loss (WL) therapy in the management of type 2 diabetes (T2D). GEM is a paradigm shift in the lifestyle management of T2D that focuses on reducing postnutrient glucose excursions, rather than reducing weight. We now present the 13-month follow-up results. RESEARCH DESIGN AND METHODS: The initial study sample of 172 were 30-80 years old, had T2D for ≤10 years, an HbA1c ≥6.8% (51 mmol/mol), and were not using insulin. Participants were randomized to 6 hours of group treatment, either to WL or one of three versions of GEM. GEM groups differed in degree of blood glucose (BG) feedback provided during treatment: no recommended feedback, systematic capillary BG feedback before and after nutrient intake and physical activity, or continuous glucose monitoring. Since these GEM groups did not differ in pre-post improvement they were combined for initial and current analyses. Of those who completed the 3-month postassessment, 100% and 96% of the WL and GEM participants completed the 13-month follow-up assessment. RESULTS: Pre to follow-up within-group comparisons indicated WL participants sustained improvement in body mass index (BMI) (-0.9±1.4, p=0.001). GEM participants continued to benefit in their HbA1c (-0.5±1.4, p<0.001), BMI (-1±1, p<0.001), high-density lipoprotein (p<0.001), reduction of carbohydrate ingestion (p<0.001), self-monitoring of blood glucose satisfaction (p<0.001) and frequency (p<0.001), diabetes knowledge (p<0.001), diabetes empowerment (p<0.001), and both diabetes distress emotional (p=0.009) and regimen (p=0.001) subscales. Forty-two percent and 52% of WL and GEM participants, respectively, were classified as responders (individuals whose A1c dropped by at least -0.5%), with a mean HbA1c reduction of -1.2% and -1.5%. Neither WL nor GEM responders differed from non-responders in baseline demographics, psychological or disease severity variables. While WL responders could not be predicted, 73% of GEM responders were predicted by post minus pretreatment reductions of HbA1c, diabetes medication and BMI. CONCLUSIONS: While WL sustained improvement in BMI, GEM sustained benefits across a broad range of physical, behavioral and psychological parameters, beneficial for clinicians and adults with T2D. This may be especially relevant for primary care physicians who manage about 90% of patients with T2D. TRIAL REGISTRATION NUMBER: NCT03196895.

Evaluating efficiency of counties in providing diabetes preventive care using data envelopment analysis.

For patients with diabetes, annual preventive care is essential to reduce the risk of complications. Local healthcare resources affect the utilization of diabetes preventive care. Our objectives were to evaluate the relative efficiency of counties in providing diabetes preventive care and explore potential to improve efficiencies. The study setting is public and private healthcare providers in US counties with available data. County-level demographics were extracted from the Area Health Resources File using data from 2010 to 2013, and individual-level information of diabetes preventive service use was obtained from the 2010 Behavioral Risk Factor Surveillance System. 1112 US counties were analyzed. Cluster analysis was used to place counties into three similar groups in terms of economic wellbeing and population characteristics. Group 1 consisted of metropolitan counties with prosperous or comfortable economic levels. Group 2 mostly consisted of non-metropolitan areas between distress and mid-tier levels, while Group 3 were mostly prosperous or comfortable counties in metropolitan areas. We used data enveopement analysis to assess efficiencies within each group. The majority of counties had modest efficiency in providing diabetes preventive care; 36 counties (57.1%), 345 counties (61.1%), and 263 counties (54.3%) were inefficient (efficiency scores < 1) in Group 1, Group 2, and Group 3, respectively. For inefficient counties, foot and eye exams were often identified as sources of inefficiency. Available health professionals in some counties were not fully utilized to provide diabetes preventive care. Identifying benchmarking targets from counties with similar resources can help counties and policy makers develop actionable strategies to improve performance.

Update on the safety of thiazolidinediones.

Diabetic patients are at increased risk for developing cardiovascular disease, and they constitute a large proportion of the global cardiovascular disease burden. Although multiple drugs exist for treating the hyperglycemia associated with diabetes, few have been shown to reduce cardiovascular risk. Great hope surrounded the arrival of the thiazolidinediones-drugs that favorably affect insulin sensitivity, inflammation, and some aspects of lipid profiles in diabetic patients. However, the cardiovascular effects of these agents are varied, and studies have suggested that they may be associated with increases in ischemic heart disease and heart failure, as well as with an increased risk for bone fracture. The following article provides a summary of important studies that have been published regarding the safety profiles of these agents. Findings from two recently published trials, RECORD and BARI 2D, are emphasized in this paper.

Minimizing Glucose Excursions (GEM) With Continuous Glucose Monitoring in Type 2 Diabetes: A Randomized Clinical Trial.

This study aimed to compare conventional medication management of type 2 diabetes (T2D) to medication management in conjunction with a lifestyle intervention using continuous glucose monitoring to minimize glucose excursions. Thirty adults (63% female; mean age, 53.3 years) who were diagnosed with T2D for less than 11 years (mean, 5.6 years), had glycated A1c (HbA1c) ≥ 7.0% (51 mmol/mol) (mean 8.8%, [73 mmol/mol]), and were not using insulin, were randomly assigned in a 1:2 ratio to routine care (RC) or 4 group sessions of glycemic excursion minimization plus real-time CGM (GEMCGM). Assessments at baseline and 5 months included a physical exam, metabolic and lipid panels, a review of diabetes medications, and psychological questionnaires. For the week following assessments, participants wore a blinded activity monitor and completed 3 days of 24-hour dietary recall. A subgroup also wore a blinded CGM. GEMCGM participants significantly improved HbA1c (from 8.9% to 7.6% [74-60 mmol/mol] compared with 8.8% to 8.7% [73-72 mmol/mol] for RC (P = .03). Additionally, GEMCGM reduced the need for diabetes medication (P = .01), reduced carbohydrate consumption (P = .009), and improved diabetes knowledge (P = .001), quality of life (P = .01) and diabetes distress (P = .02), and trended to more empowerment (P = .05) without increasing dietary fat, lipids, or hypoglycemia. Confirming our prior research, GEMCGM appears to be a safe, effective lifestyle intervention option for adults with suboptimally controlled T2D who do not take insulin.

Glycemic excursion minimization in the management of type 2 diabetes: a novel intervention tested in a randomized clinical trial.

INTRODUCTION: This study of adults with type 2 diabetes employed a non-inferiority hypothesis to investigate whether an innovative lifestyle focused on minimizing postnutrient blood glucose (BG) excursions (glycemic excursion minimization (GEM)) would be equivalent or superior to conventional weight loss (WL) therapy in regard to reducing HbA1c, and superior to WL when investigating physical, behavioral and psychological secondary outcomes. The impact of BG feedback on GEM efficacy was also investigated. RESEARCH DESIGN AND METHODS: 178 adults with type 2 diabetes for ≤10 years, HbA1c ≥6.8%, and not using insulin were randomized to WL (n=40) or one of three versions of GEM. Didactic (GEM-D, n=39) taught participants to choose low-glycemic load foods, reduce sedentary time and increase moderate routine physical activity. GEM-S (n=51) received GEM-D and systematically measured BG before and after meals and physical activity to educate and motivate food and activity choices. GEM-C (n=48) received GEM-D with continuous glucose monitoring feedback. All participants received 6 hours of group training and BG and activity monitors. Before and 3 months after treatment, participants were assessed for HbA1c, lipids, weight, routine physical activity, nutrition, depression, diabetes empowerment and distress. RESULTS: GEM versions did not differ in primary or secondary outcomes, so they were combined for analyses. While WL reduced body mass index (BMI) (p=0.005), GEM demonstrated a greater reduction in HbA1c (p=0.005), BMI (p=0.013), carbohydrate intake (p=0.001), BG response to a glucose challenge (p=0.02), and cardiovascular risk (p=0.003). Only GEM participants significantly improved diabetes empowerment, diabetes distress, depressive symptoms, steps/day, and active hours and reduced calories/day. Neither intervention had negative side effects. CONCLUSIONS: GEM is an effective alternative to WL with respect to physical, behavioral and psychosocial outcomes. TRIAL REGISTRATION NUMBER: NCT03196895.

Trends in Uninsured Rates Before and After Medicaid Expansion in Counties Within and Outside of the Diabetes Belt.

OBJECTIVE: To examine trends in uninsured rates between 2012 and 2016 among low-income adults aged <65 years and to determine whether the Patient Protection and Affordable Care Act (ACA), which expanded Medicaid, impacted insurance coverage in the Diabetes Belt, a region across 15 southern and eastern U.S. states in which residents have high rates of diabetes. RESEARCH DESIGN AND METHODS: Data for 3,129 U.S. counties, obtained from the Small Area Health Insurance Estimates and Area Health Resources Files, were used to analyze trends in uninsured rates among populations with a household income ≤138% of the federal poverty level. Multivariable analysis adjusted for the percentage of county populations aged 50-64 years, the percentage of women, Distressed Communities Index value, and rurality. RESULTS: In 2012, 39% of the population in the Diabetes Belt and 34% in non-Belt counties were uninsured (P < 0.001). In 2016 in states where Medicaid was expanded, uninsured rates declined rapidly to 13% in Diabetes Belt counties and to 15% in non-Belt counties. Adjusting for county demographic and economic factors, Medicaid expansion helped reduce uninsured rates by 12.3% in Diabetes Belt counties and by 4.9% in non-Belt counties. In 2016, uninsured rates were 15% higher for both Diabetes Belt and non-Belt counties in the nonexpansion states than in the expansion states. CONCLUSIONS: ACA-driven Medicaid expansion was more significantly associated with reduced uninsured rates in Diabetes Belt than in non-Belt counties. Initial disparities in uninsured rates between Diabetes Belt and non-Belt counties have not existed since 2014 among expansion states. Future studies should examine whether and how Medicaid expansion may have contributed to an increase in the use of health services in order to prevent and treat diabetes in the Diabetes Belt.

Reduced daily risk of glycemic variability: comparison of exenatide with insulin glargine.

BACKGROUND: Conventional methods describing daily glycemic variability (i.e., standard deviation and coefficient of variation) do not express risk. Low and High Blood Glucose Indices (LBGI and HBGI, respectively) and Average Daily Risk Range (ADRR) are parameters derived from self-monitored blood glucose (SMBG) data that quantify risk of glycemic excursions and temporal aspects of variability. In the present study, variability parameters were used to assess effects of exenatide and insulin glargine on risk of acute blood glucose extremes. METHODS: New (LBGI, HBGI, and ADRR) and conventional variability analyses were applied retrospectively to SMBG data from patients with type 2 diabetes suboptimally controlled with metformin and a sulfonylurea plus exenatide or insulin glargine as a next therapeutic step. Exenatide- (n = 282) and insulin glargine-treated (n = 267) patients were well matched. RESULTS: Exenatide treatment reduced ADRR overall (exenatide, mean +/- SEM, 16.33 +/- 0.45; insulin glargine, 18.54 +/- 0.49; P = 0.001). Seventy-seven percent of exenatide-treated patients were at low risk for glucose variability compared with 62% of glargine-treated patients (P = 0.00023). LBGI for exenatide remained minimal for all categories and significantly lower than glargine for all comparisons, and HBGI for exenatide remained low or moderate for all categories and significantly lower than glargine after the morning and evening meals. Reduced variability in exenatide-treated patients was shown by conventional methods but provided no indications of risk. CONCLUSIONS: Average glycemic control was similar for both treatment groups. However, exenatide treatment minimized risk for glycemic variability and extremes to a greater degree than insulin glargine treatment.

Optimizing Postprandial Glucose Management in Adults With Insulin-Requiring Diabetes: Report and Recommendations.

Faster-acting insulins, new noninsulin drug classes, more flexible insulin-delivery systems, and improved continuous glucose monitoring devices offer unprecedented opportunities to improve postprandial glucose (PPG) management and overall care for adults with insulin-treated diabetes. These developments led the Endocrine Society to convene a working panel of diabetes experts in December 2018 to assess the current state of PPG management, identify innovative ways to improve self-management and quality of life, and align best practices to current and emerging treatment and monitoring options. Drawing on current research and collective clinical experience, we considered the following issues for the ∼200 million adults worldwide with type 1 and insulin-requiring type 2 diabetes: (i) the role of PPG management in reducing the risk of diabetes complications; (ii) barriers preventing effective PPG management; (iii) strategies to reduce PPG excursions and improve patient quality of life; and (iv) education and clinical tools to support endocrinologists in improving PPG management. We concluded that managing PPG to minimize or prevent diabetes-related complications will require elucidating fundamental questions about optimal ways to quantify and clinically assess the metabolic dysregulation and consequences of the abnormal postprandial state in diabetes and recommend research strategies to address these questions. We also identified practical strategies and tools that are already available to reduce barriers to effective PPG management, optimize use of new and emerging clinical tools, and improve patient self-management and quality of life.

Behavioral Strategies to Lower Postprandial Glucose in Those with Type 2 Diabetes May Also Lower Risk of Coronary Heart Disease.

INTRODUCTION: Efforts to lower glycosylated hemoglobin (A1c) in patients with type 2 diabetes (T2D) are intended to reduce the risk of diabetic complications, but A1c is not the only factor contributing to this risk. Consequently, we re-analyzed published data from a broad-spectrum lifestyle intervention that lowered A1c to assess its effectiveness in lowering the overall risk of two complications of T2D, namely, coronary heart disease (CHD) and stroke. METHODS: Data from 37 adults who participated in a randomized clinical trial of a lifestyle intervention intended to reduce postprandial glucose (PPG) were re-analyzed for their pre- and post-treatment risk of CHD and stroke using the T2D-specific UK Prospective Diabetes Study (UKPDS) v2.0 risk algorithm. RESULTS: Compared to participants who received routine care, those using the lifestyle intervention had a significantly greater reduction in 10-year risk for CHD, but not for stroke. CONCLUSION: These secondary analyses suggest that broad-spectrum lifestyle interventions that focus on lowering PPG may lower the risk of future CHD, which could guide future research. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02432391.