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Aims: The aim was to evaluate the effect of extended use of the Omnipod® 5 Automated Insulin Delivery (AID) System in adults with type 2 diabetes and suboptimal glycaemic control., Materials and Methods: Following an 8-week single-arm, multicentre, outpatient trial of AID in adults with type 2 diabetes and baseline HbA1c ≥ 8% (≥ 64 mmol/mol), participants were given the opportunity to continue use of the AID system in a 26-week (~6 month) extension phase. The primary safety endpoints were percentage of time with sensor glucose ≥ 250 mg/dL and < 54 mg/dL. Additional glycaemic measures, including percentage of time in range (TIR) (70-180 mg/dL) and HbA1c, were evaluated. The use of non-insulin anti-hyperglycaemic medications was permitted throughout the entire study., Results: During the initial 8-week study, participants (N = 22) achieved a decrease in percentage of time ≥ 250 mg/dL from 27.4% ± 21.0% to 10.5% ± 8.8% (p < 0.0001), which further decreased to 9.7% ± 9.2% during the extension phase (p = 0.0002 vs. standard therapy). Percentage of time < 54 mg/dL remained low from standard therapy through extension (median [interquartile range] 0.00% [0.00%, 0.06%] vs. 0.02% [0.00%, 0.05%], p > 0.05). HbA1c decreased by 1.6% ± 1.2% (15.5 ± 13.1 mmol/mol, p < 0.0001) and TIR increased by 22.4% ± 19.2% (p < 0.0001) from standard therapy through extension with no significant change in body mass index and without an observed increase in total daily insulin requirements., Conclusions: These longer-term findings of Omnipod 5 AID System use demonstrate the potential value of AID in helping people with type 2 diabetes reach glycaemic targets., (© 2024 Insulet Corporation and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To assess the efficacy and safety of sotagliflozin, a dual inhibitor of sodium-glucose co-transporters 1 and 2, in adults with type 2 diabetes (T2D) and stage 3 chronic kidney disease (CKD3)., Materials and Methods: This phase 3, randomized, placebo-controlled trial evaluated sotagliflozin 200 and 400 mg in 787 patients with T2D and an estimated glomerular filtration rate of 30-59 ml/min/1.73m 2 . The primary objective was superiority of week 26 HbA1c reductions with sotagliflozin versus placebo. Secondary endpoints included changes in other glycaemic and renal endpoints overall and in CKD3 subgroups., Results: At 26 weeks, the placebo-adjusted mean change in HbA1c (from a baseline of 8.3% ± 1.0%) was -0.1% (95% CI: -0.2% to 0.05%; P = .2095) and -0.2% (-0.4% to -0.09%; P = .0021) in the sotagliflozin 200 and 400 mg groups, respectively. Significant reductions in fasting plasma glucose and body weight, but not systolic blood pressure, were observed. Among patients with at least A2 albuminuria at week 26, the urine albumin-creatinine ratio (UACR) was reduced with both sotagliflozin doses relative to placebo. At week 52, UACR was reduced with sotagliflozin 200 mg in the CKD3B group. Adverse events (AEs), including serious AEs, were similar between the treatment groups., Conclusions: After 26 weeks, HbA1c was significantly reduced with sotagliflozin 400 but not 200 mg compared with placebo in this CKD3 cohort. UACR in patients with at least A2 albuminuria was reduced with each of the two doses at 26 weeks, but changes were not sustained at week 52. The safety findings were consistent with previous reports (NCT03242252)., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Time spent in glycemic target range (time in range [TIR]; plasma glucose 70-180 mg/dL [3.9-10.0 mmol/L]) as a surrogate endpoint for long-term diabetes-related outcomes requires validation. This post hoc analysis investigated the association between TIR, derived from 8-point glucose profiles (derived TIR [dTIR]) at 12 months, and time to cardiovascular or severe hypoglycemic episodes in people with type 2 diabetes in the DEVOTE trial. At 12 months, dTIR was significantly negatively associated with time to first major adverse cardiovascular event ( P  = 0.0087), severe hypoglycemic episode ( P  < 0.0001), or microvascular event ( P  = 0.024). A nonsignificant trend was seen toward association between 12-month hemoglobin A1c (HbA1c) and these outcomes, but this was no longer seen after addition of dTIR to the model. The results support targeting TIR >70% and suggest dTIR could be used in addition to, or in some instances in place of, HbA1c as a clinical biomarker. Trial registration details: ClinicalTrials.gov, NCT01959529.

Objective: Automated insulin delivery (AID) has rarely been studied in adults with type 2 diabetes. We tested the feasibility of using AID for type 2 diabetes with the Omnipod 5 System in a multicenter outpatient trial., Research Design and Methods: Participants previously were using either basal-only or basal-bolus insulin injections, with or without the use of a continuous glucose monitor (CGM), and had a baseline HbA1c ≥8% (≥64 mmol/mol). Participants completed 2 weeks of CGM sensor data collection (blinded for those not previously using CGM) with their standard therapy (ST), then transitioned to 8 weeks of AID. Participants who previously used basal-only injections used the AID system in manual mode for 2 weeks before starting AID. Antihyperglycemic agents were continued at clinician discretion. Primary safety outcomes were percentage of time with sensor glucose ≥250 mg/dL and <54 mg/dL during AID. Additional outcomes included HbA1c and time in target range (TIR) (70-180 mg/dL)., Results: Participants (N = 24) had a mean (± SD) age of 61 ± 8 years, baseline HbA1c of 9.4% ± 0.9% (79 ± 10 mmol/mol), and diabetes duration of 19 ± 9 years. Percentage of time with sensor glucose ≥250 mg/dL decreased with AID by 16.9% ± 16.2% (P < 0.0001), whereas percentage of time at <54 mg/dL remained low during both ST and AID (median [interquartile range] 0.0% [0.00%, 0.06%] vs. 0.00% [0.00%, 0.03%]; P = 0.4543). HbA1c (± SD) decreased by 1.3% ± 0.7% (14 ± 8 mmol/mol; P < 0.0001) and TIR increased by 21.9% ± 15.2% (P < 0.0001) without a significant change in total daily insulin or BMI with AID., Conclusions: Findings from this feasibility trial of AID in adults with type 2 diabetes with suboptimal glycemic outcomes justify further evaluation of this technology in this population., (© 2023 by the American Diabetes Association.)

Background/objectives: Routine use of vitamin D supplements has increased substantially in the United States. However, the safety and tolerability of long-term use of high-dose vitamin D are not known. We assessed the safety and tolerability of high-dose, daily vitamin D 3 in the vitamin D and type 2 diabetes (D2d) study., Subjects/methods: In total, 2423 overweight/obese persons with prediabetes were randomized in a double-blind manner to either 4000 IU of vitamin D 3 (the tolerable upper intake level for adults by the National Academy of Medicine) taken daily or matching placebo. All participants were included in this analysis. Incident adverse events (AE) were ascertained 4 times a year at in-person visits (twice a year) and interim remote encounters (twice a year) and were defined as untoward or unfavorable medical occurrences. Serious adverse events (SAE) included death, life-threatening events, and hospitalizations., Results: A total of 8304 AEs occurred during 3 years of follow-up and were less frequent in the vitamin D group compared to placebo (Incidence Rate Ratio [IRR] = 0.94; 95% Confidence Interval (CI) 0.90, 0.98). The overall frequency of protocol-specified AEs of interest, which included nephrolithiasis, hypercalcemia, hypercalciuria, or low estimated glomerular filtration rate, was low and did not differ by group. There were no significant between-group differences in total SAEs (IRR = 0.96 (0.81, 1.14))., Conclusion: Vitamin D 3 supplementation at 4000 IU per day was safe and well tolerated among overweight/obese participants at high risk for diabetes who were appropriately monitored for safety. In this population, this dose of vitamin D 3 did not increase risk of AEs or SAEs, including those previously associated with vitamin D such as hypercalcemia, hypercalciuria, or nephrolithiasis., Clinical Trial Registration: ClinicalTrials.gov NCT01942694, prospectively registered September 16, 2013., (© 2022. The Author(s).)

Objective: To explore the effect of discontinuing continuous glucose monitoring (CGM) after 8 months of CGM use in adults with type 2 diabetes treated with basal without bolus insulin., Research Design and Methods: This multicenter trial had an initial randomization to either real-time CGM or blood glucose monitoring (BGM) for 8 months followed by 6 months in which the BGM group continued to use BGM ( n = 57) and the CGM group was randomly reassigned either to continue CGM ( n = 53) or discontinue CGM with resumption of BGM for glucose monitoring ( n = 53)., Results: In the group that discontinued CGM, mean time in range (TIR) 70-180 mg/dL, which improved from 38% before initiating CGM to 62% after 8 months of CGM, decreased after discontinuing CGM to 50% at 14 months (mean change from 8 to 14 months -12% [95% CI -21% to -3%], P = 0.01). In the group that continued CGM use, little change was found in TIR from 8 to 14 months (baseline 44%, 8 months 56%, 14 months 57%, mean change from 8 to 14 months 1% [95% CI -11% to 12%], P = 0.89). Comparing the two groups at 14 months, the adjusted treatment group difference in mean TIR was -6% (95% CI -16% to 4%, P = 0.20)., Conclusions: In adults with type 2 diabetes treated with basal insulin who had been using real-time CGM for 8 months, discontinuing CGM resulted in a loss of about one-half of the initial gain in TIR that had been achieved during CGM use., (© 2021 by the American Diabetes Association.)

Aims: To assess the efficacy and safety of sotagliflozin, a dual inhibitor of sodium-glucose cotransporter-1 and -2, in adults with type 2 diabetes (T2D) and stage 4 chronic kidney disease (CKD4)., Materials and Methods: This 52-week, phase 3, randomized (1:1:1), placebo-controlled trial evaluated sotagliflozin 200 mg and sotagliflozin 400 mg once daily in 277 patients with T2D and estimated glomerular filtration rate (eGFR) 15 to 30 mL/min/1.73 m 2 . The primary endpoint was glycated haemoglobin (HbA1c) reduction with sotagliflozin 400 mg versus placebo at 26 weeks. A hierarchical statistical testing approach was used., Results: The baseline mean HbA1c was 65 ± 12 mmol/mol (8.1% ± 1.1%), systolic blood pressure (SBP) was 144 ± 15 mmHg, and eGFR was 24 ± 4 mL/min/1.73m 2 . Placebo-adjusted changes with sotagliflozin 400 mg were -3 mmol/mol (-0.3%; 95% confidence interval -7 to 0.6 [-0.6 to 0.05]; P = 0.096) and -8 mmol/mol (-0.7%; -13 to -3 [-1.2 to -0.2]; P = 0.003) in HbA1c at Weeks 26 and 52, respectively, -1.5 kg (-3.0 to -0.1) in body weight at Week 26, -5.4 mmHg (-9.4 to -1.3) in SBP at Week 12, and -0.3 mL/min/1.73 m 2 (-2.1 to 1.6; P = 0.776) in eGFR at Week 52. Over 52 weeks, 11.8%, 5.4% and 3.3% of patients receiving placebo and sotagliflozin 200 and 400 mg, respectively, required rescue therapy for hyperglycaemia. Adverse events (AEs) occurred in 82.8%, 86.2% and 81.1% of patients and serious cardiovascular AEs occurred in 12.9%, 3.2% and 4.4% of patients in the placebo and sotagliflozin 200 and 400 mg groups, respectively., Conclusions: After 26 weeks, HbA1c reductions with sotagliflozin were not statistically significant versus placebo in adults with T2D and CKD4. The 52-week safety profile was consistent with results of the SCORED outcomes trial (NCT03242018)., (© 2021 John Wiley & Sons Ltd.)

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycemia, behavioral considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management, and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that health care professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors., (© 2021 by the American Diabetes Association.)

Importance: Continuous glucose monitoring (CGM) has been shown to be beneficial for adults with type 2 diabetes using intensive insulin therapy, but its use in type 2 diabetes treated with basal insulin without prandial insulin has not been well studied., Objective: To determine the effectiveness of CGM in adults with type 2 diabetes treated with basal insulin without prandial insulin in primary care practices., Design, Setting, and Participants: This randomized clinical trial was conducted at 15 centers in the US (enrollment from July 30, 2018, to October 30, 2019; follow-up completed July 7, 2020) and included adults with type 2 diabetes receiving their diabetes care from a primary care clinician and treated with 1 or 2 daily injections of long- or intermediate-acting basal insulin without prandial insulin, with or without noninsulin glucose-lowering medications., Interventions: Random assignment 2:1 to CGM (n = 116) or traditional blood glucose meter (BGM) monitoring (n = 59)., Main Outcomes and Measures: The primary outcome was hemoglobin A1c (HbA1c) level at 8 months. Key secondary outcomes were CGM-measured time in target glucose range of 70 to 180 mg/dL, time with glucose level at greater than 250 mg/dL, and mean glucose level at 8 months., Results: Among 175 randomized participants (mean [SD] age, 57 [9] years; 88 women [50%]; 92 racial/ethnic minority individuals [53%]; mean [SD] baseline HbA1c level, 9.1% [0.9%]), 165 (94%) completed the trial. Mean HbA1c level decreased from 9.1% at baseline to 8.0% at 8 months in the CGM group and from 9.0% to 8.4% in the BGM group (adjusted difference, -0.4% [95% CI, -0.8% to -0.1%]; P = .02). In the CGM group, compared with the BGM group, the mean percentage of CGM-measured time in the target glucose range of 70 to 180 mg/dL was 59% vs 43% (adjusted difference, 15% [95% CI, 8% to 23%]; P < .001), the mean percentage of time at greater than 250 mg/dL was 11% vs 27% (adjusted difference, -16% [95% CI, -21% to -11%]; P < .001), and the means of the mean glucose values were 179 mg/dL vs 206 mg/dL (adjusted difference, -26 mg/dL [95% CI, -41 to -12]; P < .001). Severe hypoglycemic events occurred in 1 participant (1%) in the CGM group and in 1 (2%) in the BGM group., Conclusions and Relevance: Among adults with poorly controlled type 2 diabetes treated with basal insulin without prandial insulin, continuous glucose monitoring, as compared with blood glucose meter monitoring, resulted in significantly lower HbA1c levels at 8 months., Trial Registration: ClinicalTrials.gov Identifier: NCT03566693.

Aims: To evaluate the efficacy and safety of dapagliflozin (DAPA) + saxagliptin (SAXA) compared with glimepiride (GLIM) in patients with type 2 diabetes who were inadequately controlled [glycated haemoglobin (HbA1c) 7.5-10.5% (58-91 mmol/mol)] on metformin monotherapy., Materials and Methods: This 52-week, multicentre, double-blind, active-controlled study (NCT02419612) randomized (1:1) patients on metformin to add-on DAPA 10 mg + SAXA 5 mg (n = 227) or GLIM 1-6 mg (titrated; n = 217). The primary efficacy endpoint was change in HbA1c from baseline to week 52., Results: Baseline mean ± standard deviation of age, duration of diabetes and HbA1c were 56.1 ± 9.7 years, 7.8 ± 6.4 years and 8.5% ± 0.8% (69 ± 9.0 mmol/mol), respectively. Adjusted mean change from baseline in HbA1c was -1.35% (-14.8 mmol/mol) with DAPA + SAXA versus -0.98% (-10.7 mmol/mol) with GLIM (P <0.001). Changes from baseline in body weight and systolic blood pressure were -3.1 kg and -2.6 mmHg with DAPA + SAXA versus +1.0 kg (P <0.001) and +1.0 mmHg (P = 0.007) with GLIM. More patients achieved HbA1c <7.0% (53 mmol/mol) (44.3% vs. 34.3%; P = 0.044), and fewer patients required treatment intensification (1.3% vs. 8.8%; P = 0.002) with DAPA + SAXA than with GLIM., Conclusions: Compared with GLIM, concurrent addition of DAPA + SAXA significantly improved glycaemic control, body weight and other metabolic parameters in patients inadequately controlled on metformin. Trial: NCT02419612, ClinicalTrials.gov., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

This post hoc analysis of an 18-week randomized trial explored the utility of calculating baseline glycated haemoglobin (HbA1c), postprandial glucose (PPG) increments and nocturnal glucose change in predicting efficacy and safety outcomes in response to bolus insulin intensification in people with type 2 diabetes (T2D). Analyses were conducted on 236 participants with T2D receiving metformin: 116 received fast-acting insulin aspart (faster aspart) basal-bolus therapy and 120 received basal-only insulin. Participants were grouped according to baseline HbA1c, PPG increments and nocturnal glucose change variables; analyses were performed on the end-of-trial treatment differences between "high" and "low" baseline values. The change from baseline in end-of-trial mean HbA1c and mean PPG increments was in favour of faster aspart across all subgroups. Significantly greater treatment differences were observed in participants with high (vs. low) baseline nocturnal glucose change and PPG increments. For baseline HbA1c, significantly greater treatment differences were observed for change in end-of-trial PPG increments, but not end-of-trial HbA1c. In conclusion, both nocturnal glucose change and PPG increments may be more useful than HbA1c for identifying subgroups of people with T2D who would most benefit from bolus intensification., (© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Sodium-glucose cotransporter (SGLT) inhibitors are new oral antidiabetes medications shown to effectively reduce glycated hemoglobin (A1C) and glycemic variability, blood pressure, and body weight without intrinsic properties to cause hypoglycemia in people with type 1 diabetes. However, recent studies, particularly in individuals with type 1 diabetes, have demonstrated increases in the absolute risk of diabetic ketoacidosis (DKA). Some cases presented with near-normal blood glucose levels or mild hyperglycemia, complicating the recognition/diagnosis of DKA and potentially delaying treatment. Several SGLT inhibitors are currently under review by the U.S. Food and Drug Administration and European regulatory agencies as adjuncts to insulin therapy in people with type 1 diabetes. Strategies must be developed and disseminated to the medical community to mitigate the associated DKA risk. This Consensus Report reviews current data regarding SGLT inhibitor use and provides recommendations to enhance the safety of SGLT inhibitors in people with type 1 diabetes., (© 2019 by the American Diabetes Association.)

Objective: The impact of weight loss intervention on disability-free life expectancy in adults with diabetes is unknown. We examined the impact of a long-term weight loss intervention on years spent with and without physical disability., Research Design and Methods: Overweight or obese adults with type 2 diabetes age 45-76 years ( n = 5,145) were randomly assigned to a 10-year intensive lifestyle intervention (ILI) or diabetes support and education (DSE). Physical function was assessed annually for 12 years using the 36-Item Short Form Health Survey. Annual incidence of physical disability, mortality, and disability remission were incorporated into a Markov model to quantify years of life spent active and physically disabled., Results: Physical disability incidence was lower in the ILI group (6.0% per year) than in the DSE group (6.8% per year) (incidence rate ratio 0.88 [95% CI 0.81-0.96]), whereas rates of disability remission and mortality did not differ between groups. ILI participants had a significant delay in moderate or severe disability onset and an increase in number of nondisabled years ( P < 0.05) compared with DSE participants. For a 60-year-old, this effect translates to 0.9 more disability-free years (12.0 years [95% CI 11.5-12.4] vs. 11.1 years [95% CI 10.6-11.7]) but no difference in total years of life. In stratified analyses, ILI increased disability-free years of life in women and participants without cardiovascular disease (CVD) but not in men or participants with CVD., Conclusions: Long-term lifestyle interventions among overweight or obese adults with type 2 diabetes may reduce long-term disability, leading to an effect on disability-free life expectancy but not on total life expectancy., (© 2018 by the American Diabetes Association.)

The first systems for continuous glucose monitoring (CGM) became available over 15 years ago. Many then believed CGM would revolutionize the use of intensive insulin therapy in diabetes; however, progress toward that vision has been gradual. Although increasing, the proportion of individuals using CGM rather than conventional systems for self-monitoring of blood glucose on a daily basis is still low in most parts of the world. Barriers to uptake include cost, measurement reliability (particularly with earlier-generation systems), human factors issues, lack of a standardized format for displaying results, and uncertainty on how best to use CGM data to make therapeutic decisions. This Scientific Statement makes recommendations for systemic improvements in clinical use and regulatory (pre- and postmarketing) handling of CGM devices. The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes., (© 2017 by the American Diabetes Association and Springer-Verlag.)

Intentional weight loss is an important treatment option for overweight persons with type 2 diabetes mellitus (DM), but the effects on long-term fracture risk are not known. The purpose of this Look AHEAD analysis was to evaluate whether long-term intentional weight loss would increase fracture risk in overweight or obese persons with DM. Look AHEAD is a multicenter, randomized clinical trial. Recruitment began in August 2001 and follow-up continued for a median of 11.3 years at 16 academic centers. A total of 5145 persons aged 45 to 76 years with DM were randomized to either an intensive lifestyle intervention (ILI) with reduced calorie consumption and increased physical activity designed to achieve and maintain ≥7% weight loss or to diabetes support and education intervention (DSE). Incident fractures were ascertained every 6 months by self-report and confirmed with central adjudication of medical records. The baseline mean age of participants was 59 years, 60% were women, 63% were white, and the mean BMI was 36 kg/m 2 . Weight loss over the intervention period (median 9.6 years) was 6.0% in ILI and 3.5% in DSE. A total of 731 participants had a confirmed incident fracture (358 in DSE versus 373 in ILI). There were no statistically significant differences in incident total or hip fracture rates between the ILI and DSE groups. However, compared to the DSE group, the ILI group had a statistically significant 39% increased risk of a frailty fracture (HR 1.39; 95% CI, 1.02 to 1.89). An intensive lifestyle intervention resulting in long-term weight loss in overweight/obese adults with DM was not associated with an overall increased risk of incident fracture but may be associated with an increased risk of frailty fracture. When intentional weight loss is planned, consideration of bone preservation and fracture prevention is warranted. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Objectives: This study examined the relationship between medication adherence, cost sharing measured as out-of-pocket spending, and total annual spending in Medicare beneficiaries with type 2 diabetes (T2D) to evaluate whether pharmacy cost-sharing programs have the potential to decrease adherence. These programs may unintentionally increase the risk of medical complications and may result in higher spending overall., Study Design: This retrospective study used 2006 to 2009 Medicare claims data. The sample included patients 65 years or older with T2D (at least 1 claim with International Classification of Diseases, 9th Revision, Clinical Modification codes 250.x0 and 250.x2 and at least 1 antidiabetes drug claim)., Methods: Medication adherence was measured as proportion of days covered over the first 12 months of observation. Spending and adherence outcomes were defined in deciles., Results: The sample included 12,305 patient-year observations. Pharmacy spending for patients in the most adherent (10th) decile was 59% higher than that for patients in the least adherent (1st) decile ($4839 vs $3046). Yet, patients in the 10th decile had 49% lower total ($12,531 vs $24,468) and 64% lower medical spending ($7692 vs $21,421) than patients in the 1st decile. Greater out-of-pocket spending was correlated with lower adherence and higher total and medical spending., Conclusions: This study describes a widespread variation in medication adherence, pharmacy cost sharing, and medical spending in a sample of Medicare beneficiaries with T2D. We found that lower adherence was correlated with higher cost sharing in the Medicare population, perhaps because of unobserved confounding factors. However, the existing literature on patients with employer-sponsored insurance suggests some of this correlation may be indicative of causal relationships.

Physical activity (PA) has numerous health benefits, particularly for those with diabetes. However, rates of long-term PA participation are often poor., Purpose: This study examined the effect of an intensive lifestyle intervention (ILI) on objectively assessed PA for a 4-yr period among older adults with type 2 diabetes., Methods: Data from 2400 participants (age = 59.3 ± 6.9 yr, body mass index = 36.1 ± 5.9 kg·m) with accelerometry data from the Look AHEAD trial were included in the analyses. Participants randomized to ILI were instructed to reduce caloric intake and progress to ≥175 min·wk of moderate-to-vigorous-intensity PA (MVPA), whereas those randomized to Diabetes Support and Education (DSE) served as the control group. PA was measured at baseline, year 1, and year 4 using an RT3 accelerometer, and bout-related MVPA (PA ≥3 METs, accumulated in bouts of ≥10 min in duration) was calculated., Results: Despite no differences at baseline (ILI = 93.4 ± 152.7 vs DSE = 88.4 ± 143.6 min·wk), bout-related MVPA was significantly greater in ILI compared with DSE at year 1 (151.0 ± 213.5 vs 87.5 ± 145.1 min·wk, P < 0.0001) and year 4 (102.9 ± 195.6 vs 73.9 ± 267.5 min·wk, P < 0.001), and more ILI participants achieved ≥175 min·wk at year 1 (29.1% vs 16.3%, P < 0.001) and year 4 (18.3% vs 10.0%, P < 0.001). Forty-one percent of ILI participants who achieved ≥175 min·wk at year 1 maintained this threshold of PA at year 4. However, the majority of ILI participants never achieved the ≥175 min·wk threshold., Conclusions: When measured objectively and compared with DSE, ILI engaged in significantly more bout-related MVPA for a 4-yr period. However, future intervention strategies should target the large percentage of individuals who fail to reach the MVPA goal as result of a lifestyle intervention., Competing Interests: The remaining authors have no conflicts of interest to report.

Objective: To formulate clinical practice guidelines for the use of continuous glucose monitoring and continuous subcutaneous insulin infusion in adults with diabetes., Participants: The participants include an Endocrine Society-appointed Task Force of seven experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology co-sponsored this guideline., Evidence: The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned one systematic review and used the best available evidence from other published systematic reviews and individual studies., Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines., Conclusions: Continuous subcutaneous insulin infusion and continuous glucose monitoring have an important role in the treatment of diabetes. Data from randomized controlled trials are limited on the use of medical devices, but existing studies support the use of diabetes technology for a wide variety of indications. This guideline presents a review of the literature and practice recommendations for appropriate device use.

Background: Type 2 diabetes and cardiovascular disease impose substantial clinical and economic burdens for seniors (age 65 and above) and the Medicare program. Intensive Behavioral Counseling (IBC) interventions like the National Diabetes Prevention Program (NDPP), have demonstrated effectiveness in reducing excess body weight and lowering or delaying morbidity onset. This paper estimated the potential health implications and medical savings of a digital version of IBC modeled after the NDPP., Methods and Findings: Participants in this digital IBC intervention, the Omada program, include 1,121 overweight or obese seniors with additional risk factors for diabetes or heart disease. Weight changes were objectively measured via participant use of a networked weight scale. Participants averaged 6.8% reduction in body weight within 26 weeks, and 89% of participants completed 9 or more of the 16 core phase lessons. We used a Markov-based microsimulation model to simulate the impact of weight loss on future health states and medical expenditures over 10 years. Cumulative per capita medical expenditure savings over 3, 5 and 10 years ranged from $1,720 to 1,770 (3 years), $3,840 to $4,240 (5 years) and $11,550 to $14,200 (10 years). The range reflects assumptions of weight re-gain similar to that seen in the DPP clinical trial (lower bound) or minimal weight re-gain aligned with age-adjusted national averages (upper bound). The estimated net economic benefit after IBC costs is $10,250 to $12,840 cumulative over 10 years. Simulation outcomes suggest reduced incidence of diabetes by 27-41% for participants with prediabetes, and stroke by approximately 15% over 5 years., Conclusions: A digital, remotely-delivered IBC program can help seniors at risk for diabetes and cardiovascular disease achieve significant weight loss, reduces risk for diabetes and cardiovascular disease, and achieve meaningful medical cost savings. These findings affirm recommendations for IBC coverage by the U.S. Preventive Services Task Force., Competing Interests: This study is sponsored by Omada Health, Inc. M.P. and C.M.C.S. are employees of the study sponsor. F.C., W.S., T.M.D., and S.H.B. provide paid consulting services to the study sponsor for this and other research. A.L.P. is a scientific advisor to the study sponsor and receives stock options from the study sponsor. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Older adults with type 1 diabetes (T1D) or insulin-using type 2 diabetes (iT2D) are at high risk for severe hypoglycemic episodes. Real-time continuous glucose monitoring (RT-CGM) in this population may reduce this risk, but when patients switch to Medicare at age 65, RT-CGM is no longer a covered benefit. We developed a survey to examine health and quality of life (QOL) benefits of RT-CGM in seniors (age ≥ 65)., Methods: Two groups of seniors with T1D or iT2D-current RT-CGM users (n = 210) and RT-CGM "hopefuls" (patients who wanted but could not obtain RT-CGM due to lack of insurance coverage; n = 75)-completed an online survey. The survey examined history of hypoglycemic experiences as well as current quality of life (QOL), including generic and diabetes-specific measures., Results: Current users reported fewer moderate (P < .01) and fewer severe hypoglycemic episodes (P < .01) over the past 6 months than "hopefuls" and greater reductions over time in hypoglycemic events requiring the assistance of another, ER visits, and paramedic visits to the home (in all cases, P < .01). Regarding QOL, current users reported significantly better well-being (P < .001), less hypoglycemic fear (P < .05), and less diabetes distress (P < .05) than "hopefuls.", Conclusions: These data suggest that RT-CGM use in seniors is associated with reductions in episodes of severe hypoglycemia and improved QOL, suggesting that restrictive access to RT-CGM in the Medicare age population may have deleterious health, economic, and QOL consequences., (© 2016 Diabetes Technology Society.)

Objective: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication., Research Design and Methods: Cases identified incidentally are described., Results: We identified 13 episodes of SGLT-2 inhibitor-associated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers., Conclusions: SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: Digital therapeutics are evidence-based behavioral treatments delivered online that can increase accessibility and effectiveness of health care. However, few studies have examined long-term clinical outcomes of digital therapeutics., Objective: The objective of this study was to conduct a 2-year follow-up on participants in the Internet-based Prevent diabetes prevention program pilot study, specifically examining the effects on body weight and A1c, which are risk factors for diabetes development., Methods: A quasi-experimental research design was used, including a single-arm pre- and post-intervention assessment of outcomes. Participants underwent a 16-week weight loss intervention and an ongoing weight maintenance intervention. As part of the program, participants received a wireless scale, which was used to collect body weight data on an ongoing basis. Participants also received A1c test kits at baseline, 0.5 year, 1 year, and 2-year time points., Results: Participants previously diagnosed with prediabetes (n=220) were originally enrolled in the pilot study. A subset of participants (n=187) met Centers for Disease Control and Prevention (CDC) criteria for starting the program (starters), and a further subset (n=155) met CDC criteria for completing the program (completers) and were both included in analyses. Program starters lost an average of 4.7% (SD 0.4) of baseline body weight after 1 year and 4.2% (SD 0.8) after 2 years, and reduced A1c by mean 0.38% (SD 0.07) after 1 year and 0.43% (SD 0.08) after 2 years. Program completers lost mean 4.9% (SD 0.5) of baseline body weight after 1 year and 4.3% (SD 0.8) after 2 years, and reduced A1c by 0.40% (SD 0.07) after 1 year and 0.46% (SD 0.08) after 2 years. For both groups, neither 2-year weight loss nor A1c results were significantly different from 1-year results., Conclusions: Users of the Prevent program experienced significant reductions in body weight and A1c that are maintained after 2 years. Contrary to the expected progression from prediabetes to diabetes over time, average A1c levels continued to show an average regression from within the prediabetic range (5.7%-6.4%) initially to the normal range (<5.7%) after 2 years. Further investigation is warranted to test digital therapeutics as a scalable solution to address national diabetes and cardiovascular disease prevention efforts.

Purpose: To examine whether patient-reported indicators of medical home performance are associated with health-related quality of life (HRQOL) among adults with type 2 diabetes., Methods: Cross-sectional survey of 540 patients with Medicaid insurance and type 2 diabetes in Los Angeles County. The Primary Care Assessment Tool was used to measure seven features of medical home performance. The EuroQol EQ-5D-3L (EQ-5D) was used to measure HRQOL., Results: Higher total medical home performance was correlated with better overall HRQOL. A one-point change in total medical home score was associated with a 0.06-point higher score on the EQ-5D index [95 % confidence interval (CI): 0.01-0.11], which is a clinically meaningful difference. The total score was also significantly associated with a lower likelihood of problems on one domain of the EQ-5D (pain). Longitudinality was the only medical home feature associated with better general health status (ordered odds ratio = 1.78; 95 % CI: 1.04-3.03). The positive relationship of medical home with the EQ-5D appears to be present predominantly among women., Conclusion: Overall medical home experience is favorably associated with HRQOL among vulnerable adult patients with type 2 diabetes. Provider efforts to improve the overall medical home experience for patients may contribute to improvements in HRQOL.

Objective: To determine whether an intensive lifestyle intervention (ILI) designed to sustain weight loss and improve physical fitness in overweight or obese persons with type 2 diabetes was associated with bone loss after 4 years of follow-up., Research Design and Methods: This randomized controlled trial of intensive weight loss compared an ILI with a diabetes support and education (DSE) group among 1,309 overweight or obese subjects. Bone mineral density was assessed at baseline and after 1 year and 4 years of intervention., Results: ILI was effective in producing significant weight loss (5.3% vs. 1.8% in ILI and DSE, respectively; P < 0.01) and increased fitness (6.4% vs. -0.8%) at year 4. In men, ILI participants had a greater rate of bone loss during the first year (-1.66% vs. -0.09% per year in ILI and DSE, respectively). Differences between groups were diminished by one-half after 4 years (-0.88% vs. -0.05% per year in ILI and DSE, respectively) but remained significant (P < 0.01). The difference in rate of hip bone loss between groups over 4 years was related to increased weight loss in ILI. Among women, the rate of bone loss did not differ between ILI and DSE after 4 years., Conclusions: A 4-year weight loss intervention was significantly associated with a modest increase in bone loss at the hip in men but not in women., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: To assess the relative impact of an intensive lifestyle intervention (ILI) on use and costs of health care within the Look AHEAD trial., Research Design and Methods: A total of 5,121 overweight or obese adults with type 2 diabetes were randomly assigned to an ILI that promoted weight loss or to a comparison condition of diabetes support and education (DSE). Use and costs of health-care services were recorded across an average of 10 years., Results: ILI led to reductions in annual hospitalizations (11%, P = 0.004), hospital days (15%, P = 0.01), and number of medications (6%, P < 0.001), resulting in cost savings for hospitalization (10%, P = 0.04) and medication (7%, P < 0.001). ILI produced a mean relative per-person 10-year cost savings of $5,280 (95% CI 3,385-7,175); however, these were not evident among individuals with a history of cardiovascular disease., Conclusions: Compared with DSE over 10 years, ILI participants had fewer hospitalizations, fewer medications, and lower health-care costs., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: The patient-centered medical home has gained much traction. Little is known about the relationship between the model and specific health care processes for chronic diseases such as diabetes. This study assesses the impact of features of a medical home on diabetes care., Research Design and Methods: A cross-sectional survey of 540 patients with Medicaid (Medi-Cal) health insurance and type 2 diabetes in Los Angeles County was performed. The Primary Care Assessment Tools was used to measure seven features of medical-home performance., Results: The response rate of the patient survey was 68.9%. Patient-reported medical-home performance averaged a score of 2.85 ± 0.29 (on a 1-4 scale, with 4 equaling the best care). Patients who received more timely and thorough diabetes care reported higher medical-home performance in every feature except for the comprehensiveness-services available. For example, the first-contact access feature score was higher among patients who had an HbA1c test in the past 6 months versus those who did not (2.38 vs. 2.25; P < 0.05). Before and after adjusting for sociodemographics and health status, total medical-home performance was positively associated with each diabetes care measure. A 1-point increase in total medical-home score was associated with 4.53 higher odds of an HbA1c test in the past 6 months and 1.88 higher odds of an eye exam in the past year., Conclusions: Features consistent with higher medical-home performance are associated with improvements in patient-reported diabetes care process measures, even in this low socioeconomic status setting. The patient-centered medical-home model may help in caring for people with type 2 diabetes., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Purpose: The purpose of this study was to investigate how an intergenerational legacy of type 2 diabetes affected the knowledge, attitudes, and treatment strategies of Hispanic young adults with diabetes., Methods: Eight Hispanic young adults (ages 18-30 years) participated in a series of in-home longitudinal qualitative interviews, and 11 of their family members completed single in-home interviews, regarding their diabetes management practices. Interview transcripts were analyzed thematically by a team of researchers., Results: Five themes emerged that characterized the influence of an intergenerational legacy of diabetes on young adults: food and family (how meal preparation and eating are shared within families), doing together (activity participation is contingent on others' participation), knowledge and expectations (expectations for the future and understandings of diabetes are shaped by family members), miscarried helping (well-intentioned actions have negative consequences), and reciprocal support (children and parents support each other's diabetes care)., Conclusions: Hispanic young adults' knowledge, attitudes, and self-care practices related to diabetes are strongly influenced by the diabetes management practices of family members with diabetes, which often depart from current standards of diabetes care. Care providers should consider family members as a potentially significant influence, either positive or negative, on the diabetes self-care practices of this population., (© 2014 The Author(s).)

Purpose: The purpose of this study was to evaluate the efficacy of Prevent, an online social network-based translation of the Diabetes Prevention Program (DPP) lifestyle intervention, against the Centers for Disease Control and Prevention (CDC) Diabetes Prevention and Recognition Program (DPRP) outcome standards and weight loss outcomes of other DPP translations., Methods: Two hundred twenty participants previously diagnosed with prediabetes were recruited online and enrolled in Prevent, a DPP-based group lifestyle intervention that integrates a private online social network, weekly lessons, health coaching, and a wireless scale and pedometer. Participants underwent a core 16-week intensive lifestyle change intervention and were then offered to continue with a post-core lifestyle change maintenance intervention, with the entire intervention (core plus post-core) totaling 12 months., Results: One hundred eighty-seven participants met inclusion criteria for the core program and achieved an average of 5.0% and 4.8% weight loss at 16 weeks and 12 months, respectively. They also had a 0.37% reduction in their A1C level at final measurement. One hundred forty-four of these same participants also met inclusion criteria for the post-core program and achieved an average of 5.4% and 5.2% weight loss at 16 weeks and 12 months, respectively, and a 0.40% reduction in A1C at final measurement., Conclusion: Results indicate that Prevent meets CDC DPRP outcome standards for diabetes prevention programs and performs favorably to other DPP translations. Considering national initiatives to address the obesity and diabetes epidemics, online delivery platforms like Prevent offer an effective and scalable solution., (© 2014 The Author(s).)

Study Objective: Increasingly, low-income inner-city patients with diabetes utilize emergency departments (EDs) for acute and chronic care. We seek to determine whether a scalable, low-cost, unidirectional, text message-based mobile health intervention (TExT-MED) improves clinical outcomes, increases healthy behaviors, and decreases ED utilization in a safety net population., Methods: We conducted an randomized controlled trial of 128 adult patients with poorly controlled diabetes (glycosylated hemoglobin [Hb A1C] level ≥8%) in an urban, public ED. The TExT-MED group received 2 daily text messages for 6 months in English or Spanish. The primary outcome was change in Hb A1C level. Secondary outcomes included changes in medication adherence, self-efficacy, performance of self-care tasks, quality of life, diabetes-specific knowledge, ED utilization, and patient satisfaction., Results: Hb A1C level decreased by 1.05% in the TExT-MED group compared with 0.60% in the controls (Δ0.45; 95% confidence interval [CI] -0.27 to 1.17) at 6 months. Secondary outcomes favored the TExT-MED group, with the most sizable change observed in self-reported medication adherence (as measured by the Morisky Medication Adherence Scale, an 8-point validated scale with higher scores representing better adherence), which improved from 4.5 to 5.4 in the TExT-MED group compared with a net decrease of -0.1 in the controls (Δ1.1 [95% CI 0.1 to 2.1]). Effects were larger among Spanish speakers for both medication adherence (1.1 versus -0.3; Δ1.4; 95% CI 0.2 to 2.7) and Hb A1C (-1.2% versus -0.4%) in the TExT-MED group. The proportion of patients who used emergency services trended lower in the TExT-MED group (35.9% versus 51.6%; Δ15.7%; 95% CI 9.4% to 22%). Overall, 93.6% of respondents enjoyed TExT-MED and 100% would recommend it to family/friends., Conclusion: The TExT-MED program did not result in a statistically significant improvement in Hb A1C. However, trends toward improvement in the primary outcome of Hb A1C and other secondary outcomes, including quality of life, were observed, the most pronounced being improved medication adherence. TExT-MED also decreased ED utilization. These findings were magnified in the Spanish-speaking subgroup. Technologies such as TExT-MED represent highly scalable, low-cost, and widely accessible solutions for safety-net ED populations., (Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Background and Aims: Few studies have evaluated long-term durability of glycemic control in older patients. The aim of this study was to compare durability of glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25; 75 % insulin lispro protamine suspension, 25 % insulin lispro) and once-daily insulin glargine (GL) added to oral antihyperglycemic medications in older patients (≥65 years of age)., Methods: Patients were participants in the maintenance phase of the DURABLE trial. During the initiation phase, patients with type 2 diabetes were randomized to LM75/25 or GL. After 6 months, patients with hemoglobin A1c (HbA1c) ≤7.0 % advanced to the 24-month maintenance phase. The primary objective was between-group comparison of duration of maintaining the HbA1c goal in older patients (≥65 years of age). A similar analysis was conducted for older patients achieving HbA1c ≤6.5 % in the initiation phase., Results: Median time of maintaining HbA1c goal was longer in LM75/25 versus GL (19.6 versus 15.4 months, p = 0.007) and more LM75/25 patients maintained goal versus GL (49.2 versus 30.4 %; p = 0.003). HbA1c reduction from baseline was greater in LM75/25 versus GL (-1.56 ± 0.10 versus -1.24 ± 0.11 %; p = 0.003). Post-meal glucose was significantly lower in LM75/25 versus GL (158.86 ± 3.42 versus 171.67 ± 4.51 mg/dL; p = 0.017). No differences were observed in overall and severe hypoglycemia. LM75/25 patients had higher daily insulin doses (0.41 ± 0.02 versus 0.32 ± 0.02 units/kg/day; p < 0.001) and more weight gain (5.47 ± 0.49 versus 3.10 ± 0.53 kg; p = 0.001). Similar results were generally obtained in older patients with HbA1c ≤6.5 %., Conclusions: In our evaluation of older patients from a larger trial, LM75/25 appeared to provide longer durability of glycemic control, as well as a greater number of patients maintaining HbA1c goal versus GL.

Objectives: To compare the effects of 4 years of intensive lifestyle intervention on weight, fitness, and cardiovascular disease risk factors in older and younger individuals., Design: Randomized controlled clinical trial., Setting: Sixteen U.S. clinical sites., Participants: Individuals with type 2 diabetes mellitus: 1,053 aged 65 to 76 and 4,092 aged 45 to 64., Interventions: An intensive behavioral intervention designed to promote and maintain weight loss through caloric restriction and increased physical activity was compared with diabetes mellitus support and education., Measurements: Standardized assessments of weight, fitness (based on graded exercise testing), and cardiovascular disease risk factors., Results: Over 4 years, older individuals had greater intervention-related mean weight losses (6.2%) than younger participants (5.1%; interaction P = .006) and comparable relative mean increases in fitness (0.56 vs 0.53 metabolic equivalents; interaction P = .72). These benefits were seen consistently across subgroups of older adults formed according to many demographic and health factors. Of a panel of age-related health conditions, only self-reported worsening vision was associated with poorer intervention-related weight loss in older individuals. The intensive lifestyle intervention produced mean increases in high-density lipoprotein cholesterol (2.03 mg/dL; P < .001) and decreases in glycated hemoglobin (0.21%; P < .001) and waist circumference (3.52 cm; P < .001) over 4 years that were at least as large in older as in younger individuals., Conclusion: Intensive lifestyle intervention targeting weight loss and increased physical activity is effective in overweight and obese older individuals to produce sustained weight loss and improvements in fitness and cardiovascular risk factors., (© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.)

Background: Postmarketing reports have linked exenatide use with acute pancreatitis and pancreatic cancer, but a definitive relationship has yet to be established., Subjects and Methods: We conducted a retrospective cohort analysis of patients with type 2 diabetes with employer-provided health insurance from 2007 to 2009. Multivariate models estimated the association between exenatide use and acute pancreatitis and pancreatic cancer. We required at least 1 year of exenatide exposure in the pancreatic cancer analysis. Sensitivity analyses were conducted that quasirandomized exenatide use based on patient out-of-pocket costs., Results: Among 268,561 patients included in the acute pancreatitis analysis, only 2.6% used exenatide. Hospitalization for acute pancreatitis was rare (0.247% of patients). In unadjusted and adjusted analyses, patients who did not use exenatide were more likely to be hospitalized for acute pancreatitis (0.249% vs. 0.196% in unadjusted analysis), but the difference was not statistically significant in either analysis (P = 0.22 and P = 0.70, respectively). Among 209,306 patients in the pancreatic cancer analysis, 0.070% were diagnosed with pancreatic cancer, and 0.88% had at least 1 year of continuous exenatide exposure prior to the diagnosis. Those with exenatide exposure had higher rates of pancreatic cancer compared with those without (0.081% vs. 0.070% in unadjusted analysis). In both unadjusted and adjusted analyses, the difference was not statistically significant (P = 0.80 and P = 0.46, respectively). In sensitivity analyses, results were similar., Conclusions: We found no association between exenatide use and either hospitalization for acute pancreatitis or pancreatic cancer in a large sample of privately insured U.S. patients.

Objective: To compare Medicaid spending among patients with type 2 diabetes mellitus (T2DM) receiving exenatide or other add-on therapies., Study Design: Medicaid data in patients with T2DM were compared among those who initiated exenatide, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, or basal insulin. Patients were on a regimen of metformin and/or sulfonylurea for 30 days and continued the next-line therapy for at least 90 days., Methods: Total inpatient, outpatient, prescription, and total annual health expenditures were compared for 1 year following treatment initiation. Regression analyses were conducted to compare spending; analyses controlled for patient characteristics, year of initiation, and prior therapy. Propensity score matching was used to match patients receiving exenatide with those receiving other therapies, and analyses were repeated with matched cohorts., Results: Of 23,966 eligible patients, 1345 initiated exenatide and 22,621 initiated other therapies. In the unmatched analysis, medical spending was significantly lower in those given exenatide compared with those given other therapies for inpatient ($1945 vs $3893), prescription ($4505 vs $5714), and total costs ($11,830 vs $15,459) (P <.01 for all); outpatient spending was not significantly different ($5380 vs $5853, P = .15). In the matched analysis (n = 1345 for exenatide, n = 1345 non-exenatide), patients receiving exenatide had significantly lower spending in all 4 categories: inpatient ($1945 vs $4242), outpatient ($5380 vs $6826), prescription ($4505 vs $5878), and total ($11,830 vs $16,945) (P <.01 for all)., Conclusion: Patients with T2DM receiving exenatide had lower annual Medicaid claims costs compared with patients receiving other therapies.

Objective: Numerous mobile health (mHealth) interventions are being developed to aid in management of complex chronic medical conditions. However, the acceptance of mHealth programs by low-income, bilingual populations has not yet been evaluated. The Trial to Examine Text-based mHealth for Emergency department patients with Diabetes (TExT-MED) program is a text message-based mHealth program designed specifically for resource-poor patients with diabetes. We conducted a prospective proof-of-concept trial to assess satisfaction and preliminary effectiveness of the TExT-MED program., Research Design and Methods: A consecutive sample of adult patients in the emergency department with diabetes and a text message-capable mobile phone was enrolled in the TExT-MED program. Participants received three text messages daily for 3 weeks in English or Spanish in the following domains: educational/motivational, medication reminders, healthy living challenges, diabetes trivia, and links to free diabetes management tools., Results: Twenty-three patients with diabetes (median hemoglobin A1c, 8.9%) were enrolled in TExT-MED. In the week before TExT-MED, 56.5% of subjects reported eating fruits/vegetables daily versus 83% after, 43.5% reported exercising before versus 74% after, and 74% reported performing foot checks before versus 85% after. Self-efficacy, measured by the Diabetes Empowerment Scale-Short Form, improved from 3.9 to 4.2. Scores on the Morisky Medication Adherence Scale improved more dramatically from 3.5 to 4.75. Ninety percent of participants indicated they would like to continue the program, and 100% would recommend the program to family or friends., Conclusions: This pilot trial of the TExT-MED program demonstrated increased healthy behaviors, improved diabetes self-efficacy and medication adherence, and received excellent satisfaction scores in resource-poor, inner city patients with diabetes.

Intentional weight loss is an important component of treatment for overweight patients with type 2 diabetes, but the effects on bone density are not known. We used data from the Look AHEAD trial to determine the impact of an intensive lifestyle weight loss intervention (ILI) compared with diabetes support and education (DSE) on changes in bone mineral density (BMD) over 12 months. Overweight and obese adults with type 2 diabetes were randomly assigned to ILI or DSE. In a substudy of BMD conducted at 5 of 16 clinical centers, hip, spine, and whole body dual X-ray absorptiometry scans were obtained at baseline and 1-year later on 642 of 739 ILI and 632 of 740 DSE participants. At baseline, mean age was 58.4 years, and average body mass index was 35.2 kg/m(2). Total hip BMD T-score was <-2.5 in 1% and <-1.0 in 8%. At 1 year, weight loss was greater in ILI than DSE (-8.6% versus -0.7%), and glycemic control and fitness were also improved. Bone loss over 1 year was greater in ILI at the total hip (-1.4% versus -0.4%; p < 0.001) and femoral neck (-1.5% versus -0.8%; p = 0.009), but change in BMD for the lumbar spine and whole body did not differ between groups. In ILI, bone loss at the total hip was independently associated with weight loss in men and women and with poorer glycemic control in men, but was not associated with changes in fitness. One year of an intensive lifestyle intervention in adults with type 2 diabetes, resulting in weight loss, was associated with a modest increase in hip bone loss despite improved fitness and glycemic control., (Copyright © 2012 American Society for Bone and Mineral Research.)

Lifestyle modifications in conjunction with antidiabetes medications can produce near-normal blood glucose concentrations in patients with type 2 diabetes mellitus (T2DM). Because these patients have increased cardiovascular morbidity and mortality, treatment strategies should also address the cardiovascular aspects of the disease, including blood pressure, lipids, and body weight. Since the prevalence of these abnormalities is increasingly secondary to poor diet and sedentary lifestyles and because most patients with T2DM are overweight/obese, clinicians are encouraged to help patients reduce body weight while correcting hyperglycemia by selecting treatment options that improve both parameters. The glucose-lowering properties of insulin and sulfonylureas are well known but they are also associated with weight gain. Thiazolidinediones are associated with weight gain as well as edema. However, this weight gain may be more peripheral than central, which may mitigate the risks associated with increased body fat. Metformin, the consensus first-line drug for the treatment of patients with T2DM, is weight neutral. Newer antidiabetes agents include incretin-based medications, such as the glucagon-like peptide-1 receptor agonists, which tend to decrease weight, and the dipeptidyl peptidase-4 inhibitors, which are weight neutral.

According to the most recent data from the Centers for Disease Control, nearly 24 million Americans have type 2 diabetes mellitus (T2DM); of these, 6 million individuals with T2DM remain undiagnosed. At least 57 million more American adults are at high risk for developing T2DM by virtue of having impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both, which constitute prediabetes. Treating T2DM remains challenging, despite the availability of effective therapies. Recent data indicate that slightly more than half of the patients (~56%) with T2DM are achieving the American Diabetes Association (ADA) glycosylated hemoglobin (HbA1C) goal of <7%. A major contributing factor to the inability to maintain glycemic control in patients with T2DM is its progressive nature. There is a continuum from normoglycemia to IGT/IFG (prediabetes) to diabetes, and from uncomplicated diabetes to more difficult-to-control diabetes and diabetes with complications. This continuum has implications for treatment strategies and for the need to continually modify these strategies as the disease progresses. Understanding where the patient is on the continuum of disease may help identify mechanisms of action that can be targeted and aid in therapeutic decision-making. For example, early in the disease process, T2DM is characterized by insulin resistance and hyperinsulinemia. As such, agents that target insulin sensitivity and insulin resistance may be especially useful early in the disease process. Although the 2 main defects of T2DM are insulin resistance and pancreatic beta-cell dysfunction/failure, other aspects of its pathophysiology may be targeted to specific metabolic pathways and effects.

Type 2 diabetes is a disorder that has numerous components, including insulin resistance, an insulin secretory defect, and an increase in hepatic glucose production. Until recently, only the insulin secretory defect could be treated. Within recent years, the thiazolidinedione (TZD) class of drugs, which targets primarily insulin resistance, was released. Originally developed in Japan as triglyceride-lowering agents, TZDs were found to be more effective in lowering blood glucose levels instead. The actions of 2 TZDs--rosiglitazone and pioglitazone--are discussed, and their glucose- and nonglucose-lowering effects are explained. Four case histories are presented to illustrate various patients' responses to TZDs in clinical practice. Although TZDs have been demonstrated to be effective in dealing with many different aspects of type 2 diabetes, further study, involving multiple clinical trials, is needed.

Insulin resistance is a prime risk factor associated with atherosclerosis and thrombosis. Other risk factors include dyslipidemia, obesity, and hypertension. The constellation of those factors, which is known as the cardiovascular dysmetabolic syndrome, increases the risk of macrovascular disease. Insulin resistance may contribute directly to cardiovascular disease and may also act as a precursor of diabetes, which is also associated with an increased risk of macrovascular disease. Insulin resistance can be difficult to assess clinically, but it is invariably present in patients with type 2 diabetes, impaired fasting glucose, or impaired glucose tolerance. Treatment of insulin resistance includes diet, exercise, smoking cessation, strict control of hypertension, aggressive treatment of lipid abnormalities, and keeping the hemoglobin A1c level below 7%. New oral agents improve glycemic control for those with diabetes or insulin resistance, but their role in reducing the risk of macrovascular disease is undetermined.

Context: New criteria for the diagnosis of type 2 diabetes mellitus have recently been introduced that lowered the diagnostic fasting plasma glucose (FPG) concentration from 7.8 to 7.0 mmol/L (140 to 126 mg/dL)., Objective: To determine if individuals with diabetes diagnosed by the new FPG concentration criterion would have excessive glycosylation (elevated hemoglobin [HbA1c] levels)., Definitions: We determined the distribution of HbA1c levels in individuals using 4 classifications: (1) normal by the new criterion (FPG concentration <6.1 mmol/L [110 mg/dL]); (2) impaired fasting glucose by the new criterion (FPG concentration of 6.1-6.9 mmol/L [110-125 mg/dL]); (3) diabetes diagnosed solely by the new FPG concentration criterion of 7.0 through 7.7 mmol/L (126-139 mg/dL); and (4) diabetes diagnosed by the previous FPG concentration criterion of 7.8 mmol/L (140 mg/dL) or higher., Design: Cross-sectional analysis of 2 large data sets (NHANES III and Meta-Analysis Research Group [MRG] on the Diagnosis of Diabetes Using Glycated Hemoglobin) that contained individuals in whom FPG concentrations, 2-hour glucose concentrations using an oral glucose tolerance test, and an HbA1c level were simultaneously measured. We cross-tabulated FPG concentrations (<6.1 mmol/L [110 mg/dL], 6.1-6.9 mmol/L [110-125 mg/dL], 7.0-7.7 mmol/L [126-139 mg/dL], and > or =7.8 mmol/L [140 mg/dL]) and HbA1c levels separated into 3 intervals: normal, less than the upper limit of normal (ULN); slightly elevated, ULN to ULN plus 1%; and high, higher than ULN plus 1%., Results: Among subjects with normal FPG concentrations, HbA1c levels in the NHANES III (and the MRG) data sets were normal in 97.3% (96.2%), slightly elevated in 2.7% (3.6%), and high in 0.1% (0.2%). Among individuals with impaired fasting glucose, HbA1c concentrations were normal in 86.7% (81.4%), slightly elevated in 13.1% (16.4%), and high in 0.2% (2.2%). Among diabetic patients diagnosed by the new FPG criterion only, HbA1c levels were normal in 60.9% (59.6%), slightly elevated in 35.8% (32.8%), and high in 3.4% (7.6%). In diabetic patients diagnosed by the former FPG criterion, HbA1c levels were normal in 18.6% (16.7%), slightly elevated in 32.5% (21.0%), and high in 48.9% (62.3%)., Conclusions: About 60% of the new cohort of diabetic patients in both data sets have normal HbA1c levels. We believe that diabetes should not be diagnosed in those with FPG concentrations less than 7.8 mmol/L (140 mg/dL) unless excessive glycosylation is evident. Individuals without excessive glycosylation but with moderate elevations of FPG concentrations (6.1-7.7 mmol/L [110-139 mg/dL]) should be diagnosed as having impaired fasting glucose and treated with an appropriate diet and exercise. This diagnostic labeling achieves the goal of early intervention without subjecting these persons to the potentially negative insurance, employment, social, and psychological consequences of a diagnosis of diabetes mellitus.

Type 2 diabetes mellitus results from impaired insulin secretion and reduced peripheral insulin sensitivity. Treatment options include diet, oral antihyperglycemic agents, and insulin. Metformin, an oral biguanide, ameliorates hyperglycemia by improving peripheral sensitivity to insulin, and reducing gastrointestinal glucose absorption and hepatic glucose production. Unlike sulfonylureas, it does not stimulate insulin secretion, aggravate hyperinsulinemia, or cause hypoglycemia or weight gain (weight stabilizes or decreases). It also has beneficial effects on serum lipid profiles. In lean or overweight type 2 diabetic patients uncontrolled by diet, metformin monotherapy significantly improves glycemic control, compared with placebo, and to similar extents as sulfonylurea monotherapy. In secondary sulfonylurea failure, combination metformin-sulfonylurea treatment significantly improves glycemic control beyond that achieved with either agent along. Metformin-sulfonylurea also appears to be as effective as insulin or insulin plus sulfonylurea, suggesting that such combination therapy may obviate or substantially delay insulin therapy. Limited data suggest that metformin-insulin therapy may improve glycemic control, possibly reducing insulin requirements, in type 2 diabetic patients uncontrolled by insulin alone following secondary sulfonylurea failure. Gastrointestinal side effects are common, but usually tolerated. Lactic acidosis risk is minimal, provided that contraindications, particularly renal impairment, and prescribing guidelines are respected. Aside from elevated plasma metformin levels with cimetidine and synergistic hypoglycemia with sulfonylureas, few interactions occur. Thus, metformin is safe and effective both as monotherapy or in combination with other antihyperglycemic agents in type 2 diabetic patients requiring additional glycemic control and may be advantageous when weight control is desirable and/or hyperlipidemia exists.

No consensus exists as to the best approach for treating markedly symptomatic patients with new-onset (or diet-treated) type 2 diabetes. Therefore, based on the experience of one successful case, further studies were undertaken to determine the safety and efficacy of maximal dose glyburide (10 mg, twice daily, in patients < 65 yr of age) or half the dose (10 mg, daily, in patients > or = 65 yr of age) for treating these patients. Fifty-five patients with polyuria, polydipsia, nocturia, involuntary weight loss, and blood glucose concentrations of 300 mg/dL or greater were treated following protocols that used maximal dose ( < 65 yr of age) or half-maximal dose ( > or = 65 yr of age) sulfonylurea agent therapy. Data were collected retrospectively in 30 patients and prospectively in 25. Patients in the prospective group differed only in that more laboratory measurements were obtained, and less strict guidelines for using insulin were adopted. Data were collected in both groups at baseline and 1 week and 4 months after starting the sulfonylurea agent therapy. Patients responded rapidly with a fall in blood glucose levels from 456 +/- 12 mg/dL at baseline to 202 +/- 10 mg/dL at 1 week to 120 +/- 5 mg/dL at 4 months. Glycated hemoglobin levels fell from 18.1 +/- 0.4% at baseline to 8.1 +/- 0.2% ( P < 0.0001) at 4 months. Most patients had symptomatic improvement within 3 days. Seventeen patients had positive (small or larger) urinary ketones, and 5 had positive serum ketones. Insulin to glucose and C peptide to glucose ratios improved maximally at 1 week, indicating rapid reversal of glucotoxicity on the beta-cell. At 4 months, 11 patients were receiving diet therapy alone, 29 were receiving submaximal dose sulfonylurea agent therapy, 6 remained on maximal dose sulfonylurea agent therapy, and only 3 were receiving insulin therapy. Six patients were lost to follow-up. No patient experienced hypoglycemia in the first 2 weeks of treatment. Maximal dose sulfonylurea agent therapy is a safe and effective method for treating patients with markedly symptomatic type 2 diabetes. Patients improve rapidly and are able to avoid the immediate institution of long term insulin therapy.