Optimizing Glycemic Outcomes for Minoritized and Medically Underserved Adults Living with Type 1 Diabetes.

Individuals living with type 1 diabetes (T1D) from medically underserved communities have poorer health outcomes. Efforts to improve outcomes include a focus on team-based care, activation of behavior change, and enhancing self-management skills and practices. Advanced diabetes technologies are part of the standard of care for adults with T1D. However, health care providers often carry implicit biases and may be uncomfortable with recommending technologies to patients who have traditionally been excluded from efficacy trials or have limited real-world exposure to devices. We review the literature on this topic and provide an approach to address these issues in clinical practice.

Proof-of-concept Application of Continuous Glucose Monitoring Data Analytics to Identify Diabetes Glucotypes.

Background: In this proof-of-concept study, we evaluated if monogenic diabetes resulting from mutations of the HNF-1α gene (HNF1A-MODY) has a distinctive continuous glucose monitoring (CGM) glucotype, in comparison to type 1 diabetes (T1D). Methods: Using CGM data from 5 subjects with HNF1A-MODY and 115 subjects with T1D, we calculated multiple glucose metrics, including measures of within- and between-day variability (such as coefficient variation for each hour [CVb_1h]). Results: The MODY and T1D cohorts had minimum CVb_1h of 11.3 ± 4.4 and 18.0 ± 4.9, respectively (P = .02) and maximum CVb_1h of 33.9 ± 5.0 and 50.3 ± 10, respectively (P < .001). All subjects with HNF1A-MODY had a minimum %CVb_1h ≤ 17.3% and maximum %CVb_1h ≤ 37.1%. In contrast, only 12 of 115 subjects with T1D had both a minimum and maximum %CVb_1h below these thresholds (P < .001). Conclusion: HNF1A- MODY is characterized by a low hourly, between-day glucose variability. CGM-derived glucose metrics may have potential applicability for screening for atypical diabetes phenotypes in the T1D population.

Sensor-augmented insulin pump therapy: results of the first randomized treat-to-target study.

BACKGROUND: The objective of the study was to evaluate the clinical effectiveness and safety of a device that combines an insulin pump with real-time continuous glucose monitoring (CGM), compared to using an insulin pump with standard blood glucose monitoring systems. METHODS: This 6-month, randomized, multicenter, treat-to-target study enrolled 146 subjects treated with continuous subcutaneous insulin infusion between the ages of 12 and 72 years with type 1 diabetes and initial A1C levels of >or=7.5%. Subjects were randomized to pump therapy with real-time CGM (sensor group [SG]) or to pump therapy and self-monitoring of blood glucose only (control group [CG]). Clinical effectiveness and safety were evaluated. RESULTS: A1C levels decreased (P<0.001) from baseline (8.44+/-0.70%) in both groups (SG, -0.71+/-0.71%; CG, -0.56+/-0.072%); however, between-group differences did not achieve significance. SG subjects showed no change in mean hypoglycemia area under the curve (AUC), whereas CG subjects showed an increase (P=0.001) in hypoglycemia AUC during the blinded periods of the study. The between-group difference in hypoglycemia AUC was significant (P<0.0002). Greater than 60% sensor utilization was associated with A1C reduction (P=0.0456). Fourteen severe hypoglycemic events occurred (11 in the SG group and three in the CG group, P=0.04). CONCLUSIONS: A1C reduction was no different between the two groups. Subjects in the CG group had increased hypoglycemia AUC and number of events during blinded CGM use; however, there was no increase in hypoglycemia AUC or number of events in the SG group. Subjects with greater sensor utilization showed a greater improvement in A1C levels.

Changes in HbA1c and Weight Following Transition to Continuous Subcutaneous Insulin Infusion Therapy in Adults With Type 1 Diabetes.

BACKGROUND: Historically, intensive insulin therapy for type 1 diabetes (T1D) has improved glycemic control at the risk of adverse weight gain. The impact of continuous subcutaneous insulin infusion therapy (CSII) on weight in the current era remains unknown. We assessed changes in hemoglobin A1c (HbA1c) and weight in adults with T1D transitioning to CSII at 2 diabetes centers in Denmark and the United States. METHODS: Patients with T1D, aged ≥18 years, managed with multiple daily injections (MDI) who transitioned to CSII between 2002 and 2013 were identified using electronic health record data from the Steno Diabetes Center (n = 600) and Joslin Diabetes Center (n = 658). Changes in HbA1c and weight after 1 year was assessed overall and by baseline HbA1c cut points. Multivariate regression assessed correlates of HbA1c reduction. RESULTS: In adults with T1D transitioning to CSII, clinically significant HbA1c reductions were found in patients with baseline HbA1c 8.0-8.9% (Steno, -0.7%; Joslin, -0.4%) and baseline HbA1c ≥9.0% (Steno, -1.1%; Joslin, -0.9%) ( P < .005 for all). Overall, there was no significant change in weight after 1 year at either center. Modest (<2%) weight gain was noted in patients with baseline HbA1c ≥9% at Steno (1.1 ± 0.3 kg, P < .0001) and Joslin (1.7 ± 1.1, P < .005). In multivariate models, HbA1c reduction was associated with higher HbA1c, older age, female sex at Steno ( R2 = .28, P < .005), but only higher baseline HbA1c at Joslin ( R2 = .19, P < .005). CONCLUSION: Adults with T1D with suboptimal glycemic control significantly improved HbA1c without a negative impact on weight 1 year after transitioning from MDI to CSII.

Optimized Mealtime Insulin Dosing for Fat and Protein in Type 1 Diabetes: Application of a Model-Based Approach to Derive Insulin Doses for Open-Loop Diabetes Management.

OBJECTIVE: To determine insulin dose adjustments required for coverage of high-fat, high-protein (HFHP) meals in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Ten adults with T1D received low-fat, low-protein (LFLP) and HFHP meals with identical carbohydrate content, covered with identical insulin doses. On subsequent occasions, subjects repeated the HFHP meal with an adaptive model-predictive insulin bolus until target postprandial glycemic control was achieved. RESULTS: With the same insulin dose, the HFHP increased the glucose incremental area under the curve over twofold (13,320 ± 2,960 vs. 27,092 ± 1,709 mg/dL ⋅ min; P = 0.0013). To achieve target glucose control following the HFHP, 65% more insulin was required (range 17%-124%) with a 30%/70% split over 2.4 h. CONCLUSIONS: This study demonstrates that insulin dose calculations need to consider meal composition in addition to carbohydrate content and provides the foundation for new insulin-dosing algorithms to cover meals of varying macronutrient composition.

Impact of fat, protein, and glycemic index on postprandial glucose control in type 1 diabetes: implications for intensive diabetes management in the continuous glucose monitoring era.

BACKGROUND: Continuous glucose monitoring highlights the complexity of postprandial glucose patterns present in type 1 diabetes and points to the limitations of current approaches to mealtime insulin dosing based primarily on carbohydrate counting. METHODS: A systematic review of all relevant biomedical databases, including MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials, was conducted to identify research on the effects of dietary fat, protein, and glycemic index (GI) on acute postprandial glucose control in type 1 diabetes and prandial insulin dosing strategies for these dietary factors. RESULTS: All studies examining the effect of fat (n = 7), protein (n = 7), and GI (n = 7) indicated that these dietary factors modify postprandial glycemia. Late postprandial hyperglycemia was the predominant effect of dietary fat; however, in some studies, glucose concentrations were reduced in the first 2-3 h, possibly due to delayed gastric emptying. Ten studies examining insulin bolus dose and delivery patterns required for high-fat and/or high-protein meals were identified. Because of methodological differences and limitations in experimental design, study findings were inconsistent regarding optimal bolus delivery pattern; however, the studies indicated that high-fat/protein meals require more insulin than lower-fat/protein meals with identical carbohydrate content. CONCLUSIONS: These studies have important implications for clinical practice and patient education and point to the need for research focused on the development of new insulin dosing algorithms based on meal composition rather than on carbohydrate content alone.

Assessing the Effect of Personalized Diabetes Risk Assessments During Ophthalmologic Visits on Glycemic Control: A Randomized Clinical Trial.

IMPORTANCE: Optimization of glycemic control is critical to reduce the number of diabetes mellitus-related complications, but long-term success is challenging. Although vision loss is among the greatest fears of individuals with diabetes, comprehensive personalized diabetes education and risk assessments are not consistently used in ophthalmologic settings. OBJECTIVE: To determine whether the point-of-care measurement of hemoglobin A(1c) (HbA(1c)) and personalized diabetes risk assessments performed during retinal ophthalmologic visits improve glycemic control as assessed by HbA(1c) level. DESIGN, SETTING, AND PARTICIPANTS: Ophthalmologist office-based randomized, multicenter clinical trial in which investigators from 42 sites were randomly assigned to provide either a study-prescribed augmented diabetes assessment and education or the usual care. Adults with type 1 or 2 diabetes enrolled into 2 cohorts: those with a more-frequent-than-annual follow-up (502 control participants and 488 intervention participants) and those with an annual follow-up (368 control participants and 388 intervention participants). Enrollment was from April 2011 through January 2013. INTERVENTIONS: Point-of-care measurements of HbA1c, blood pressure, and retinopathy severity; an individualized estimate of the risk of retinopathy progression derived from the findings from ophthalmologic visits; structured comparison and review of past and current clinical findings; and structured education with immediate assessment and feedback regarding participant's understanding. These interventions were performed at enrollment and at routine ophthalmic follow-up visits scheduled at least 12 weeks apart. MAIN OUTCOMES AND MEASURES: Mean change in HbA(1c) level from baseline to 1-year follow-up. Secondary outcomes included body mass index, blood pressure, and responses to diabetes self-management practices and attitudes surveys. RESULTS: In the cohort with more-frequent-than-annual follow-ups, the mean (SD) change in HbA(1c) level at 1 year was -0.1% (1.5%) in the control group and -0.3% (1.4%) in the intervention group (adjusted mean difference, -0.09% [95% CI, -0.29% to 0.12%]; P = .35). In the cohort with annual follow-ups, the mean (SD) change in HbA(1c) level was 0.0% (1.1%) in the control group and -0.1% (1.6%) in the intervention group (mean difference, -0.05% [95% CI, -0.27% to 0.18%]; P = .63). Results were similar for all secondary outcomes. CONCLUSIONS AND RELEVANCE: Long-term optimization of glycemic control is not achieved by a majority of individuals with diabetes. The addition of personalized education and risk assessment during retinal ophthalmologic visits did not result in a reduction in HbA(1c) level compared with usual care over 1 year. These data suggest that optimizing glycemic control remains a substantive challenge requiring interventional paradigms other than those examined in our study. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01323348.

A developmental perspective on the challenges of diabetes education and care during the young adult period.

There is increasing recognition that the patient education and care provided to young adults with chronic physical illnesses, including type 1 diabetes, is inattentive to the complex developmental issues facing the older adolescent transitioning into the young adult period [Pediatrics 110 (2002) 1307]. In this paper, we present a clinical perspective on the challenge of improving diabetes education and care during the young adult period focusing on the importance of the developmental changes-cognitive, social, emotional, educational, and familial-that occur during this transitional stage of life. This developmental perspective on young adulthood provides a conceptual framework to better understand the young adult's "readiness" for engagement in intensive medical therapy. We review factors such as the timing and context of diabetes care and education that may be important determinants of young adults' ultimate success in becoming independent managers of their health care during this difficult transition. Developmentally-based practice principles for the young adult period are presented which include: assessing the patient's expectation at transition, building the relationship, working with families, assessing barriers to care, and formulating treatment plans and goals.

Development of the Likelihood of Low Glucose (LLG) algorithm for evaluating risk of hypoglycemia: a new approach for using continuous glucose data to guide therapeutic decision making.

The objective was to develop an analysis methodology for generating diabetes therapy decision guidance using continuous glucose (CG) data. The novel Likelihood of Low Glucose (LLG) methodology, which exploits the relationship between glucose median, glucose variability, and hypoglycemia risk, is mathematically based and can be implemented in computer software. Using JDRF Continuous Glucose Monitoring Clinical Trial data, CG values for all participants were divided into 4-week periods starting at the first available sensor reading. The safety and sensitivity performance regarding hypoglycemia guidance "stoplights" were compared between the LLG method and one based on 10th percentile (P10) values. Examining 13 932 hypoglycemia guidance outputs, the safety performance of the LLG method ranged from 0.5% to 5.4% incorrect "green" indicators, compared with 0.9% to 6.0% for P10 value of 110 mg/dL. Guidance with lower P10 values yielded higher rates of incorrect indicators, such as 11.7% to 38% at 80 mg/dL. When evaluated only for periods of higher glucose (median above 155 mg/dL), the safety performance of the LLG method was superior to the P10 method. Sensitivity performance of correct "red" indicators of the LLG method had an in sample rate of 88.3% and an out of sample rate of 59.6%, comparable with the P10 method up to about 80 mg/dL. To aid in therapeutic decision making, we developed an algorithm-supported report that graphically highlights low glucose risk and increased variability. When tested with clinical data, the proposed method demonstrated equivalent or superior safety and sensitivity performance.

Experiences of health care transition voiced by young adults with type 1 diabetes: a qualitative study.

OBJECTIVE: This qualitative study aimed to explore the experience of transition from pediatric to adult diabetes care reported by posttransition emerging adults with type 1 diabetes (T1D), with a focus on preparation for the actual transfer in care. METHODS: Twenty-six T1D emerging adults (mean age 26.2±2.5 years) receiving adult diabetes care at a single center participated in five focus groups stratified by two levels of current glycemic control. A multidisciplinary team coded transcripts and conducted thematic analysis. RESULTS: FOUR KEY THEMES ON THE PROCESS OF TRANSFER TO ADULT CARE EMERGED FROM A THEMATIC ANALYSIS: 1) nonpurposeful transition (patients reported a lack of transition preparation by pediatric providers for the transfer to adult diabetes care); 2) vulnerability in the college years (patients conveyed periods of loss to follow-up during college and described health risks and diabetes management challenges specific to the college years that were inadequately addressed by pediatric or adult providers); 3) unexpected differences between pediatric and adult health care systems (patients were surprised by the different feel of adult diabetes care, especially with regards to an increased focus on diabetes complications); and 4) patients' wish list for improving the transition process (patients recommended enhanced pediatric transition counseling, implementation of adult clinic orientation programs, and peer support for transitioning patients). CONCLUSION: Our findings identify modifiable deficiencies in the T1D transition process and underscore the importance of a planned transition with enhanced preparation by pediatric clinics as well as developmentally tailored patient orientation in the adult clinic setting.

Dietary fat acutely increases glucose concentrations and insulin requirements in patients with type 1 diabetes: implications for carbohydrate-based bolus dose calculation and intensive diabetes management.

OBJECTIVE: Current guidelines for intensive treatment of type 1 diabetes base the mealtime insulin bolus calculation exclusively on carbohydrate counting. There is strong evidence that free fatty acids impair insulin sensitivity. We hypothesized that patients with type 1 diabetes would require more insulin coverage for higher-fat meals than lower-fat meals with identical carbohydrate content. RESEARCH DESIGN AND METHODS: We used a crossover design comparing two 18-h periods of closed-loop glucose control after high-fat (HF) dinner compared with low-fat (LF) dinner. Each dinner had identical carbohydrate and protein content, but different fat content (60 vs. 10 g). RESULTS: Seven patients with type 1 diabetes (age, 55 ± 12 years; A1C 7.2 ± 0.8%) successfully completed the protocol. HF dinner required more insulin than LF dinner (12.6 ± 1.9 units vs. 9.0 ± 1.3 units; P = 0.01) and, despite the additional insulin, caused more hyperglycemia (area under the curve >120 mg/dL = 16,967 ± 2,778 vs. 8,350 ± 1,907 mg/dL⋅min; P < 0001). Carbohydrate-to-insulin ratio for HF dinner was significantly lower (9 ± 2 vs. 13 ± 3 g/unit; P = 0.01). There were marked interindividual differences in the effect of dietary fat on insulin requirements (percent increase significantly correlated with daily insulin requirement; R(2) = 0.64; P = 0.03). CONCLUSIONS: This evidence that dietary fat increases glucose levels and insulin requirements highlights the limitations of the current carbohydrate-based approach to bolus dose calculation. These findings point to the need for alternative insulin dosing algorithms for higher-fat meals and suggest that dietary fat intake is an important nutritional consideration for glycemic control in individuals with type 1 diabetes.

Health care transition in young adults with type 1 diabetes: barriers to timely establishment of adult diabetes care.

OBJECTIVE: To examine barriers to health care transition reported by young adults with type 1 diabetes and associations between barriers and prolonged gaps between pediatric and adult diabetes care. METHODS: We surveyed young adults aged 22 to 30 years with type 1 diabetes about their transition experiences, including barriers to timely establishment of adult diabetes care. We evaluated relationships between barriers and gaps in care using multivariate logistic regression. RESULTS: The response rate was 53% (258 of 484 eligible subjects). Respondents (62% female) were 26.7 ± 2.4 years old and transitioned to adult diabetes care at 19.5 ± 2.9 years. Reported barriers included lack of specific adult provider referral name (47%) or contact information (27%), competing life priorities (43%), difficulty getting an appointment (41%), feeling upset about leaving pediatrics (24%), and insurance problems (10%). In multivariate analysis, barriers most strongly associated with gaps in care >6 months were lack of adult provider name (odds ratio [OR], 6.1; 95% confidence interval [CI], 3.0-12.7) or contact information (OR, 5.3; 95% CI, 2.0-13.9), competing life priorities (OR, 5.2; 95% CI, 2.7-10.3), and insurance problems (OR, 3.5; 95% CI, 1.2-10.3). Overall, respondents reporting ≥1 moderate/major barrier (48%) had 4.7-fold greater adjusted odds of a gap in care >6 months (95% CI, 2.8-8.7). CONCLUSION: Significant barriers to transition, such as a lack of specific adult provider referrals, may be addressed with more robust preparation by pediatric providers and care coordination. Further study is needed to evaluate strategies to improve young adult self-care in the setting of competing life priorities.

Health care transition in patients with type 1 diabetes: young adult experiences and relationship to glycemic control.

OBJECTIVE: To examine characteristics of the transition from pediatric to adult care in emerging adults with type 1 diabetes and evaluate associations between transition characteristics and glycemic control. RESEARCH DESIGN AND METHODS: We developed and mailed a survey to evaluate the transition process in emerging adults with type 1 diabetes, aged 22 to 30 years, receiving adult diabetes care at a single center. Current A1C data were obtained from the medical record. RESULTS: The response rate was 53% (258 of 484 eligible). The mean transition age was 19.5 ± 2.9 years, and 34% reported a gap >6 months in establishing adult care. Common reasons for transition included feeling too old (44%), pediatric provider suggestion (41%), and college (33%). Less than half received an adult provider recommendation and <15% reported having a transition preparation visit or receiving written transition materials. The most recent A1C was 8.1 ± 1.3%. Respondents who felt mostly/completely prepared for transition had lower likelihood of a gap >6 months between pediatric and adult care (adjusted odds ratio 0.47 [95% CI 0.25-0.88]). In multivariate analysis, pretransition A1C (ß = 0.49, P < 0.0001), current age (ß = -0.07, P = 0.03), and education (ß = -0.55, P = 0.01) significantly influenced current posttransition A1C. There was no independent association of transition preparation with posttransition A1C (ß = -0.17, P = 0.28). CONCLUSIONS: Contemporary transition practices may help prevent gaps between pediatric and adult care but do not appear to promote improvements in A1C. More robust preparation strategies and handoffs between pediatric and adult care should be evaluated.

Myocardial infarction triggers chronic cardiac autoimmunity in type 1 diabetes.

Patients with type 1 diabetes (T1D) suffer excessive morbidity and mortality after myocardial infarction (MI) that is not fully explained by the metabolic effects of diabetes. Acute MI is known to trigger a profound innate inflammatory response with influx of mononuclear cells and production of proinflammatory cytokines that are crucial for cardiac repair. We hypothesized that these same pathways might exert "adjuvant effects" and induce pathological responses in autoimmune-prone T1D hosts. Here, we show that experimental MI in nonobese diabetic mice, but not in control C57BL/6 mice, results in a severe post-infarction autoimmune (PIA) syndrome characterized by destructive lymphocytic infiltrates in the myocardium, infarct expansion, sustained cardiac autoantibody production, and T helper type 1 effector cell responses against cardiac (α-)myosin. PIA was prevented by inducing tolerance to α-myosin, demonstrating that immune responses to cardiac myosin are essential for this disease process. Extending these findings to humans, we developed a panel of immunoassays for cardiac autoantibody detection and found autoantibody positivity in 83% post-MI T1D patients. We further identified shared cardiac myosin autoantibody signatures between post-MI T1D patients and nondiabetic patients with myocarditis, which were absent in post-MI type 2 diabetic patients, and confirmed the presence of myocarditis in T1D by cardiac magnetic resonance imaging techniques. These data provide experimental and clinical evidence for a distinct post-MI autoimmune syndrome in T1D. Our findings suggest that PIA may contribute to worsened post-MI outcomes in T1D and highlight a role for antigen-specific immunointervention to selectively block this pathway.

The nuts and bolts of achieving end points with real-time continuous glucose monitoring.

Real-time continuous glucose monitoring (RT-CGM) provides detailed information on glucose patterns and trends and promises to be a major advance in diabetes care. To derive full potential benefit from RT-CGM, the patient needs to be skilled in diabetes self-management. In addition, several key concepts and issues need to be addressed in training patients to use RT-CGM. These include 1) the implications of the physiologic lag between interstitial and capillary blood glucose levels and 2) the increased risk among RT-CGM users for hypoglycemia related to blind postprandial bolusing. Patients need to understand the importance of calibrating during steady-state conditions to improve sensor accuracy. In addition, they need to use fingerstick measurements for treatment decision-making when the glucose level is changing rapidly, i.e., conditions when physiologic lag can lead to a marked discrepancy between blood and interstitial glucose. Consideration of "insulin on board" and the impact of the glycemic index of different foodstuffs on postprandial glucose patterns can help minimize the risk for hypoglycemia from supplemental boluses taken to correct postprandial hyperglycemia. To use continuous glucose data safely and effectively, patients need to be skilled in diabetes self-management, and the widespread adoption of RT-CGM into diabetes care will need to be coupled with comprehensive self-management education.