Between-group Difference In HbA1c Research Articles

Real-World Evidence of Off-Label Use of Commercially Automated Insulin Delivery Systems Compared to Multiple Daily Insulin Injections in Pregnancies Complicated by Type 1 Diabetes.

Aims: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) versus multiple daily insulin injections (MDI) plus continuous glucose monitoring. Methods: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR), and above (TAR) the pregnancy-specific glucose range of 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes, including baseline maternal characteristics and center. Results: One hundred twelve women were included (HCL n = 59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There was no between-group difference in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12 ± 9.06 vs. -2.16 ± 7.42 mmol/mol, P = 0.031). No difference in TIR (3.5-7.8 mmol/L) and TAR was observed between HCL and MDI users, but with a higher total insulin dose in the second trimester [+0.13 IU/kg·day)]. HCL therapy was associated with increased maternal weight gain during pregnancy (βadjusted = 3.20 kg, 95% confidence interval [CI] 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (βadjusted = 279.0 g, 95% CI 39.5-518.5) and macrosomia (ORadjusted = 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c was included in the models. Conclusions: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

Early time-restricted carbohydrate consumption vs conventional dieting in type 2 diabetes: a randomised controlled trial

Aims/hypothesisEarly time-restricted carbohydrate consumption (eTRC) is a novel dietary strategy that involves restricting carbohydrate-rich food intake to the morning and early afternoon to align with circadian variations in glucose tolerance. We examined the efficacy, feasibility and safety of eTRC in individuals with type 2 diabetes under free-living conditions.MethodsIn this randomised, parallel-arm, open label, controlled trial, participants with type 2 diabetes and overweight/obesity (age 67.2±7.9 years, 47.8% women, BMI 29.4±3.7 kg/m2, HbA1c 49±5 mmol/mol [6.6±0.5%]) were randomised, using computer-generated random numbers, to a 12 week eTRC diet or a Mediterranean-style control diet with matched energy restriction and macronutrient distribution (50% carbohydrate, 30% fat and 20% protein). The primary outcome was the between-group difference in HbA1c at 12 weeks. Body composition, 14 day flash glucose monitoring and food diary analysis were performed every 4 weeks. Mixed meal tolerance tests with mathematical beta cell function modelling were performed at baseline and after 12 weeks.ResultsTwelve (85.7%) participants in the eTRC arm and 11 (84.6%) participants in the control arm completed the study, achieving similar reductions in body weight and fat mass. The two groups experienced comparable improvements in HbA1c (−3 [−6, −0.3] mmol/mol vs −4 [−6, −2] mmol/mol, corresponding to −0.2 [−0.5, 0]% and −0.3 [−0.5, −0.1]%, respectively, p=0.386), fasting plasma glucose, flash glucose monitoring-derived glucose variability and mixed meal tolerance test-derived glucose tolerance, insulin resistance, insulin clearance and plasma glucagon levels, without changes in model-derived beta cell function parameters, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and non-esterified fatty acid levels. The two diets similarly reduced liver function markers and triglyceride levels, being neutral on other cardiometabolic and safety variables. In exploratory analyses, diet-induced changes in body weight and glucometabolic variables were not related to the timing of carbohydrate intake.Conclusions/interpretationThe proposed eTRC diet provides a feasible and effective alternative option for glucose and body weight management in individuals with type 2 diabetes, with no additional metabolic benefits compared with conventional dieting.Trial registrationClinicalTrials.gov NCT05713058FundingThis study was supported by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the Italian Society of Diabetology (SID).Graphical

Impact of a Low-Carbohydrate Compared with Low-Fat Breakfast on Blood Glucose Control in Type 2 Diabetes: A Randomized Trial

BackgroundIn type 2 diabetes (T2D), consuming carbohydrates results in a rapid and large increase in blood glucose, particularly in the morning when glucose intolerance is highest. ObjectivesWe investigated if a low-carbohydrate (LC) breakfast (∼465 kcal: 25 g protein, 8 g carbohydrates, and 37 g fat) could improve glucose control in people with T2D when compared with a low-fat control (CTL) breakfast (∼450 kcal:20 g protein, 56 g carbohydrates, and 15 g fat). MethodsParticipants with T2D (N = 121, 53% women, mean age 64 y) completed a remote 3-month parallel-group randomized controlled trial comparing a LC with standard low-fat guideline CTL breakfast. The change in HbA1c was the prespecified primary outcome. Continuous glucose monitoring, self-reported anthropometrics, and dietary information were collected for an intention-to-treat analysis. ResultsHbA1c was reduced (−0.3%; 95% CI: −0.4%, −0.1%) after 12 wks of a LC breakfast, but the between-group difference in HbA1c was of borderline statistical significance (−0.2; 95% CI: −0.4, 0.0; P = 0.06). Self-reported total daily energy (−242 kcal; 95% CI: −460, −24 kcal; P = 0.03) and carbohydrate (−73 g; 95% CI: −101, −44 g; P < 0.01) intake were lower in the LC group but the significance of this difference is unclear. Mean and maximum glucose, area under the curve, glycemic variability, standard deviation, and time above range were all significantly lower, and time in the range was significantly higher, in the LC group compared with CTL (all P < 0.05). ConclusionsAdvice and guidance to consume a LC breakfast appears to be a simple dietary strategy to reduce overall energy and carbohydrate intake and improve several continuous glucose monitoring variables when compared with a CTL breakfast in persons living with T2D.The trial was registered at clinicaltrials.gov as NCT04550468.

Using Peer Support to Prevent Diabetes: Results of a Pragmatic RCT

High-contact structured diabetes prevention programs are effective in lowering weight and HbA1cs, yet their intensity level can create barriers to participation. Peer support programs improve clinical outcomes among adults with Type 2 diabetes, but their effectiveness in diabetes prevention is unknown. This study examined whether a low-intensity peer support program improved outcomes more than enhanced usual care in a diverse population with prediabetes. The intervention was tested in a pragmatic 2-arm RCT. Participants were adults with prediabetes at three healthcare centers. Participants randomized to the enhanced usual care arm received educational materials. Participants in the Using Peer Support to Aid in Prevention and Treatment in Prediabetes arm were matched with a peer supporter: another patient who had made healthy lifestyle changes and was trained in autonomy-supportive action planning. Peer supporters were instructed to provide weekly telephone support to their peers on specific action steps toward behavioral goals for 6 months, then monthly support for 6 months. Changes in primary outcomes of weight and HbA1c and secondary outcomes of enrollment in formal diabetes prevention programs, self-reported diet, physical activity, health-specific social support, self-efficacy, motivation, and activation at 6 and 12 months were examined. Data collection occurred from October 2018 to March 2022, with analyses completed in September 2022. Among 355 randomized patients, in intention-to-treat analyses, there were no between-group differences in HbA1c or weight changes at 6 and 12 months. Using Peer Support to Aid in Prevention and Treatment in Prediabetes participants were more likely to enroll in structured programs at 6 (AOR=2.45, p=0.009) and 12 (AOR=2.21, p=0.016) months and to report eating whole grains at 6 (4.49, p=0.026) and 12 (4.22, p=0.034) months. They reported greater improvements in perceived social support for diabetes prevention behaviors at 6 (6.39, p<0.001) and 12 (5.48, p<0.001) months, with no differences in other measures. A stand-alone, low-intensity peer support program improved social support and participation in formal diabetes prevention programs but not weight or HbA1c. It will be important to examine whether peer support could effectively complement higher-intensity, structured diabetes prevention programs. This trial is registered at ClinicalTrials.gov, NCT03689530. Full protocol available at https://clinicaltrials.gov/ct2/show/NCT03689530.

Effect of routinely assessing and addressing depression and diabetes distress on clinical outcomes among adults with type 2 diabetes: a systematic review

ObjectivesThis study examined the effect of using patient-reported outcome measures (PROMs) routinely to assess and address depressive symptoms and diabetes distress among adults with type 2 diabetes.DesignA systematic review of...

With or Without Residual C-Peptide, Patients with Type 2 Diabetes Realize Glycemic Benefits from Real-Time Continuous Glucose Monitoring.

Real-time continuous glucose monitoring (RT-CGM) is superior to blood glucose monitoring (BGM) for adults with insulin-treated type 2 diabetes (T2D); however, the utility of C-peptide levels for predicting the magnitude of the glycemic benefits is controversial. Data were from a subset of 147 participants in the MOBILE study who were treated with basal-only insulin and who had baseline C-peptide levels ≥0.5 ng/mL. Participants were randomized to treatment with either RT-CGM (n = 100) or BGM (n = 47). Between-group differences in hemoglobin A1c (HbA1c) and time in range (TIR) changes were assessed. The between-group difference in HbA1c favored the RT-CGM group (by 0.58 percentage points, P = 0.004 at 3 months and by 0.42 percentage points, P = 0.04 at 8 months). TIR was 16% higher, and time >180 mg/dL was 16% lower, in the RT-CGM group at 8 months (P = 0.002 for each). In T2D managed with basal insulin, RT-CGM benefits occur for those with residual insulin secretory capacity. Clinical Trial Identifier: NCT03566693.

An Enhanced SMS Text Message-Based Support and Reminder Program for Young Adults With Type 2 Diabetes (TEXT2U): Randomized Controlled Trial.

BackgroundClinic attendance, metabolic control, engagement in self-management, and psychological health are suboptimal in young-onset (age of onset <40 years) type 2 diabetes.ObjectiveWe examined the effectiveness of an enhanced SMS text message–based support and reminder program in improving clinic attendance, metabolic control, engagement in self-management, and psychological health in young-onset type 2 diabetes.MethodsA 12-month, parallel-arm, randomized controlled trial comparing an enhanced, semipersonalized SMS text message–based intervention (incorporating 1-8 supportive and/or informative text messages per month) against standard care was conducted in a specialized clinic for young adult type 2 diabetes. The primary outcome was maintenance of 100% attendance at scheduled quarterly clinical appointments. Secondary outcomes included (1) metabolic indices, (2) pathology and self-monitored blood glucose (SMBG) data availability, and (3) psychosocial well-being.ResultsA total of 40 participants were randomized, and 32 completed their 12-month study visit. The average participant age was 32.7 (SD 5.1) years, 50% (20/40) were male, and baseline glycated hemoglobin A1c (HbA1c) was 7.3% (SD 1.9%) (56 mmol/mol, SD 20). A higher proportion of the intervention group achieved 100% attendance (12/21, 57%, vs 5/19, 26%, for the control group); Kaplan-Meier analysis demonstrated significantly greater cumulative attendance in the intervention group (P=.04). There were no between-group differences in HbA1c, BMI, lipids, or availability of pathology and SMBG data. Odds of recording an improvement in the Diabetes Empowerment Scale–Short Form score were higher in the intervention group at 6 months (odds ratio [OR] 4.3, 95% CI 1.1-17), with attenuation of this effect at study end (OR 3.1, 95% CI 0.9-11). Program acceptability was high; >90% of participants would recommend the program to new patients.ConclusionsAn enhanced SMS text message–based support and reminder program doubled scheduled clinic attendance rates for patients with young-onset type 2 diabetes. The program was highly acceptable and provided early support for patient empowerment but had no significant effect on measures of metabolic control or self-management.Trial RegistrationAustralian and New Zealand Clinical Trials Registry (ACTRN12618000479202); https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373579

Self-management in patients with type 2 diabetes: Group-based versus individual education. A systematic review with meta-analysis of randomized trails

AimPatient education is an essential component of the treatment of type 2 diabetes mellitus (T2DM). The present meta-analysis was aimed at verifying the efficacy of group-based versus individual education for self-management in patients with T2DM. Data synthesisA Medline and Embase search up to January 1st, 2021, was performed, including Randomized Controlled Trials (RCT) with duration>6 months, enrolling patients with T2DM and comparing individual-based with group-based educational programs. The primary outcome was endpoint HbA1c; secondary endpoints were lipid profile, body weight, blood pressure, patients’ adherence/knowledge, and quality of life. The weighed difference in means (WMD) and Mantel-Haenzel Odds Ratio (MH–OR), with 95% Confidence Interval (CI), were calculated.We retrieved 14 RCT. No significant between-group difference in HbA1c (WMD -0.39[-0.89; 0.09] mmol/mol, p = 0.11) was observed. At metaregression analyses, longer trial duration, higher baseline mean age and duration of diabetes, and lower baseline HbA1c were correlated with greater efficacy of group-based programs in reducing HbA1c. When analyzed separately, trials excluding insulin-treated patients showed a significant reduction of HbA1c in favor of group education. ConclusionsIn patients with T2DM, group education has similar efficacy as individual education on glucose control. Group programs are associated with an improved quality of life and patients’ knowledge. Prospero and OSF registrationID243149.

Liraglutide hospital discharge trial: A randomized controlled trial comparing the safety and efficacy of liraglutide versus insulin glargine for the management of patients with type 2 diabetes after hospital discharge.

To compare a glucagon-like peptide-1 receptor agonist with basal insulin at hospital discharge in patients with uncontrolled type 2 diabetes in a randomized clinical trial. A total of 273 patients with glycated haemoglobin (HbA1c) 7%-10% (53-86 mol/mol) were randomized to liraglutide (n = 136) or insulin glargine (n = 137) at hospital discharge. The primary endpoint was difference in HbA1c at 12 and 26 weeks. Secondary endpoints included hypoglycaemia, changes in body weight, and achievement of HbA1c <7% (53 mmol/mol) without hypoglycaemia or weight gain. The between-group difference in HbA1c at 12 weeks and 26 weeks was -0.28% (95% CI -0.64, 0.09), and at 26 weeks it was -0.55%, (95% CI -1.01, -0.09) in favour of liraglutide. Liraglutide treatment resulted in a lower frequency of hypoglycaemia <3.9 mmol/L (13% vs 23%; P = 0.04), but there was no difference in the rate of clinically significant hypoglycaemia <3.0 mmol/L. Compared to insulin glargine, liraglutide treatment was associated with greater weight loss at 26 weeks (-4.7 ± 7.7 kg vs -0.6 ± 11.5 kg; P < 0.001), and the proportion of patients with HbA1c <7% (53 mmol/mol) without hypoglycaemia was 48% versus 33% (P = 0.05) at 12 weeks and 45% versus 33% (P = 0.14) at 26 weeks in liraglutide versus insulin glargine. The proportion of patients with HbA1c <7% (53 mmol/mol) without hypoglycaemia and no weight gain was higher with liraglutide at 12 (41% vs 24%, P = 0.005) and 26 weeks (39% vs 22%; P = 0.014). The incidence of gastrointestinal adverse events was higher with liraglutide than with insulin glargine (P < 0.001). Compared to insulin glargine, treatment with liraglutide at hospital discharge resulted in better glycaemic control and greater weight loss, but increased gastrointestinal adverse events.

Effects of Metformin Added to Insulin in Adolescents with Type 1 Diabetes: An Exploratory Crossover Randomized Trial.

Background To comprehensively assess the effects of metformin added to insulin on metabolic control, insulin sensitivity, and cardiovascular autonomic function in adolescents with type 1 diabetes. Materials and Methods This was an exploratory, crossover, randomized trial conducted in adolescents with type 1 diabetes aged 12-18 years old. Participants were randomly received metformin (≤1000 mg/d) added to insulin for 24 weeks followed by insulin monotherapy for a subsequent 24 weeks or vice versa. Blood pressure, body mass index, insulin dose, estimated insulin sensitivity, glycated hemoglobin A1c (HbA1c), and lipid profiles were measured, with a 72-hour continuous glucose monitoring and 24-hour Holter monitoring performed at baseline, 24, and 50 weeks for the assessments of glucose variability and heart rate variability. Results Seventeen patients with mean ± SD age 14.4 ± 2.3 years, body mass index 18.17 ± 1.81 kg/m2, median (IQR) diabetes duration 4.50 (3.58, 6.92) years, and HbA1c 9.0% (8.5%, 9.4%) were enrolled. The between-group difference in HbA1c of 0.28% (95% CI -0.39 to 0.95%) was not significant (P = 0.40). Changes in body mass index, insulin dose, blood pressure, lipid profiles, and estimated insulin sensitivity were similar for metformin add-on vs. insulin monotherapy. Glucose variability also did not differ. Compared with insulin monotherapy, metformin add-on significantly increased multiple heart rate variability parameters. Conclusions Metformin added to insulin did not improve metabolic control or glucose variability in lean/normal-weight adolescents with type 1 diabetes. However, metformin added to insulin significantly increased heart rate variability, suggesting that metformin might improve cardiovascular autonomic function in this population.

Effect of a functional fibre supplement on glycemic control when added to a year-long medically supervised weight management program in adults with type 2 diabetes.

Soluble fibre beneficially affects metabolism but whether it can augment the reductions in glycemia induced through intensive weight management has not been extensively studied. Our objective was to examine the adjunct effect of the soluble viscous fibre PGX® on glycemic control in adults with type 2 diabetes (T2D) enrolled in a year-long medically supervised weight management program. In a placebo-controlled, double-blind study, 290 adults with overweight/obesity and T2D were randomized to receive PGX (15-20g/day) or isocaloric placebo (rice flour, 6.4-8.6g/day) as an adjunct to intensive weight management for 52weeks. The primary outcome was change in glycemic control (HbA1c). Other outcome measures included weight loss, blood lipids, blood pressure, cytokines and fecal microbiota. Compared to baseline HbA1c in PGX (7.2 ± 1.1%) and placebo (7.0 ± 0.9%) groups, there was a significant reduction at 16 and 26weeks, however, only PGX showed a significant absolute reduction of 0.23% at 52weeks; there were no between-group differences in HbA1c. At 52weeks, only PGX significantly decreased body weight compared to baseline and reduced waist circumference at all time points. Compared to baseline, only PGX showed a significant reduction in LDL cholesterol at 16 and 26weeks. PGX significantly increased the relative abundance of Collinsella, Parabacteroides and Roseburia. Adding PGX to a weight management program for individuals with T2D provides a sustained reduction in HbA1c compared to placebo. Improvements in other metabolic outcomes suggest that PGX may be a promising adjunct to weight loss programs in patients with T2D. This trial was registered at ClinicalTrials.gov as NCT01644201.

Efficacy and safety of meal-time administration of short-acting exenatide for glycaemic control in type 1 diabetes (MAG1C): a randomised, double-blind, placebo-controlled trial

In type 2 diabetes, long-acting GLP-1 receptor agonists lower fasting plasma glucose and improve glycaemic control via their insulinotropic and glucagonostatic effects. In type 1 diabetes, their efficacy as an add-on treatment to insulin therapy is modest. Short-acting GLP-1 receptor agonists also lower postprandial glucose excursions in type 2 diabetes by decelerating gastric emptying rate. We aimed to test the efficacy of a short-acting GLP-1 receptor agonist in type 1 diabetes. In the single-centre, parallel-group, randomised, double-blind, placebo-controlled MAG1C trial, patients with type 1 diabetes on multiple daily injection therapy aged 18 years and older with HbA1c 59-88 mmol/mol (7·5-10·0%) and a BMI of more than 22·0 kg/m2 were randomly assigned (1:1) through a computer-generated randomisation list to preprandial subcutaneous injection of 10 μg exenatide (Byetta) or placebo three times daily for 26 weeks as an add-on treatment to usual insulin therapy. Clinically assessed insulin titration was done by study staff. Participants and investigators were masked to treatment allocation. The primary endpoint was between-group difference in HbA1c after 26 weeks. Data were analysed with a baseline-adjusted linear mixed model in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03017352, and is completed. Between Jan 4, 2017, and Jan 16, 2019, 108 participants were randomly assigned, 54 to exenatide and 54 to placebo; 23 participants discontinued treatment (17 in the exenatide group and six in the placebo group). From a baseline-adjusted mean of 66·4 mmol/mol (95% CI 64·9-67·8 [8·2%, 8·1-8·4]), HbA1c changed by -3·2 mmol/mol (-5·0 to -1·4 [-0·3%, -0·5 to -0·1]) with exenatide and -2·1 mmol/mol (-3·7 to -0·6 [-0·2%, -0·3 to -0·1]) with placebo after 26 weeks (estimated treatment difference of -1·1 mmol/mol (-3·4 to 1·2 [-0·1%, -0·3 to 0·1]; p=0·36). Exenatide increased the number of self-reported gastrointestinal adverse events (primarily nausea [48 events among 37 patients with exenatide, nine with placebo among 9 patients]). Two serious adverse events occurred in the exenatide group, and six occurred in the placebo group (none were considered to be related to the study drug). Short-acting exenatide does not seem to have a future as a standard add-on treatment to insulin therapy in type 1 diabetes. AstraZeneca.

Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial

Chronic inflammation is believed to be a major mechanism underlying the pathophysiology of type 2 diabetes. Periodontitis is a cause of systemic inflammation. We aimed to assess the effects of periodontal treatment on glycaemic control in people with type 2 diabetes. In this 12 month, single-centre, parallel-group, investigator-masked, randomised trial, we recruited patients with type 2 diabetes, moderate-to-severe periodontitis, and at least 15 teeth from four local hospitals and 15 medical or dental practices in the UK. We randomly assigned patients (1:1) using a computer-generated table to receive intensive periodontal treatment (IPT; whole mouth subgingival scaling, surgical periodontal therapy [if the participants showed good oral hygiene practice; otherwise dental cleaning again], and supportive periodontal therapy every 3 months until completion of the study) or control periodontal treatment (CPT; supra-gingival scaling and polishing at the same timepoints as in the IPT group). Treatment allocation included a process of minimisation in terms of diabetes onset, smoking status, sex, and periodontitis severity. Allocation to treatment was concealed in an opaque envelope and revealed to the clinician on the day of first treatment. With the exception of dental staff who performed the treatment and clinical examinations, all study investigators were masked to group allocation. The primary outcome was between-group difference in HbA1c at 12 months in the intention-to-treat population. This study is registered with the ISRCTN registry, number ISRCTN83229304. Between Oct 1, 2008, and Oct 31, 2012, we randomly assigned 264 patients to IPT (n=133) or CPT (n=131), all of whom were included in the intention-to-treat population. At baseline, mean HbA1c was 8·1% (SD 1·7) in both groups. After 12 months, unadjusted mean HbA1c was 8·3% (SE 0·2) in the CPT group and 7·8% (0·2) in the IPT group; with adjustment for baseline HbA1c, age, sex, ethnicity, smoking status, duration of diabetes, and BMI, HbA1c was 0·6% (95% CI 0·3-0·9; p<0·0001) lower in the IPT group than in the CPT group. At least one adverse event was reported in 30 (23%) of 133 patients in the IPT group and 23 (18%) of 131 patients in the CPT group. Serious adverse events were reported in 11 (8%) patients in the IPT group, including one (1%) death, and 11 (8%) patients in the CPT group, including three (2%) deaths. Compared with CPT, IPT reduced HbA1c in patients with type 2 diabetes and moderate-to-severe periodontitis after 12 months. These results suggest that routine oral health assessment and treatment of periodontitis could be important for effective management of type 2 diabetes. Diabetes UK and UK National Institute for Health Research.

A Randomized Controlled Study Comparing a DPP4 Inhibitor (Linagliptin) and Basal Insulin (Glargine) in Patients With Type 2 Diabetes in Long-term Care and Skilled Nursing Facilities: Linagliptin-LTC Trial

ObjectivesSafe and easily implemented treatment regimens are needed for the management of patients with type 2 diabetes mellitus (T2DM) in long-term care (LTC) and skilled nursing facilities. DesignThis 6-month open-label randomized controlled trial compared the efficacy and safety of a DPP4 inhibitor (linagliptin) and basal insulin (glargine) in LTC residents with T2DM. SettingsThree LTC institutions affiliated with a community safety-net hospital, US Department of Veterans Affairs and Emory Healthcare System in Atlanta, Georgia. ParticipantsA total of 140 residents with T2DM treated with oral antidiabetic agents or low-dose insulin (≤0.1 U/kg/d), with fasting or premeal blood glucose (BG) > 180 mg/dL and/or HbA1c >7.5%. InterventionBaseline antidiabetic therapy, except metformin, was discontinued on trial entry. Residents were treated with linagliptin 5 mg/d (n = 67) or glargine at a starting dose of 0.1 U/kg/d (n = 73). Both groups received supplemental rapid-acting insulin before meals for BG > 200 mg/dL. MeasurementsPrimary outcome was mean difference in daily BG between groups. Main secondary endpoints included differences in frequency of hypoglycemia, glycosylated hemoglobin (HbA1c), complications, emergency department visits, and hospital transfers. ResultsTreatment with linagliptin resulted in no significant differences in mean daily BG (146 ± 34 mg/dL vs. 157 ± 36 mg/dL, P = .07) compared to glargine. Linagliptin treatment resulted in fewer mild hypoglycemic events <70 mg/dL (3% vs. 37%, P < .001), but there were no differences in BG < 54 mg/dL (P = .06) or <40 mg/dL (P = .05) compared to glargine. There were no significant between-group differences in HbA1c, length of stay, complications, emergency department visits, or hospitalizations. ConclusionTreatment with linagliptin resulted in noninferior glycemic control and in significantly lower risk of hypoglycemia compared to insulin glargine in long-term care and skilled nursing facility residents with type 2 diabetes.

Effect of repaglinide, administered two or three times daily for 3 months, on glycaemic control in Japanese patients with type 2 diabetes mellitus.

To compare the efficacy, safety and compliance of repaglinide, administered either two or three times daily, regarding glycaemic control in patients with type 2 diabetes mellitus. Japanese adults with type 2 diabetes mellitus, who had been treated without sulphonylureas or glinides for >3 months, were randomly assigned to two groups to receive either 0.25 mg repaglinide, oral, twice daily (group A) or 0.25 mg repaglinide, oral, three times daily (group B). Glycosylated haemoglobin (HbA1c), glycoalbumin (GA) and 1,5-anhydroglucitol (1,5-AG) levels were measured at 0, 1, 2 and 3 months after treatment commenced. Out of 43 patients who enrolled (group A, n = 22; group B, n = 21), 33 patients completed the trial (group A, n = 16; group B, n = 17). No significant between-group differences in HbA1c, GA, or 1,5-AG levels were seen at 1-3 months. No severe hypoglycaemic episodes or other adverse events were observed. Minimal-dose repaglinide administered twice daily was similar in efficacy and safety to three-times-daily administration, in Japanese patients with type 2 diabetes mellitus. Administration of repaglinide twice daily could be an alternative regimen for patients who cannot take repaglinide three times daily.

Impact of Remote Management of Diabetes via Computer: The 360 Study—A Proof-of-Concept Randomized Trial

Previous studies have provided limited guidance regarding the clinical efficacy and cost-effectiveness of interventions using "telemedicine" models in the management of diabetes mellitus. We conducted a study to determine if routine clinical assessments of diabetes patients could be effectively conducted via computer and telephone interaction with patients and still provide clinical results similar to traditional office care. We enrolled 100 subjects with diabetes in this 12-month, randomized, controlled, non-inferiority study. Subjects were randomized (1:1 ratio) to a control group (CG) or study group (SG). Baseline characteristics were similar. CG subjects participated in quarterly office visits; SG subjects participated in two office visits (months 6 and 12) and two telemedicine interactions (months 3 and 9). Changes in clinical measurements (hemoglobin A1c [HbA1c], blood pressure, lipids, body mass index [BMI], and body weight) and clinician time requirements were assessed. Seventy subjects completed the study (CG, n=37; SG, n=33). No significant between-group differences in HbA1c, blood pressure, lipids, or BMI were seen at 12 months. SG subjects showed significantly greater reductions in mean (SD) body weight compared with CG subjects: -5.2 (1.6) pounds versus -0.7 (1.5) pounds, respectively (P=0.04). Clinician time requirements for SG subjects were reduced by >40%. Our study demonstrated that use of a telemedicine-based treatment protocol in diabetes patients is feasible and efficient and yields similar clinical outcomes compared with traditional, clinic-based protocols. Telemedicine applications of computer software can potentially expand access to care for patients and may reduce costs for patients, providers, and payers.

Continuous subcutaneous insulin infusion versus multiple daily insulin injections in type 1 diabetes: a meta-analysis

Continuous subcutaneous insulin infusion (CSII) is considered an option for type 1 diabetic patients unsatisfactorily controlled with multiple daily injections (MDI). Short-acting analogs are superior to regular human insulin in CSII. This meta-analysis is aimed at assessing the advantages of short-acting analog-based CSII over MDI in type 1 diabetes. Randomized clinical trials (RCTs) comparing CSII (with analogs) and MDI for at least 12 weeks in type 1 diabetic patients were retrieved, assessing between-group differences in HbA1c and incidence of hypoglycemia. A total of 11 RCTs was included in the analysis. CSII was associated with a significant improvement of HbA1c in comparison with MDI (standardized difference in mean: -0.3 [-0.4;-0.1]%; P < 0.001). No significant difference was observed in the rate of severe hypoglycemic episodes. The reduction of HbA1c with CSII was evident in trials enrolling patients with mean age greater than 10 years, but not in younger children. Available data justify the use of CSII for basal-bolus insulin therapy in type 1 diabetic patients unsatisfactorily controlled with MDI.

Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Insulin Injections in Type 2 Diabetes: A Meta-analysis

Continuous Subcutaneous Insulin Infusion (CSII) improves HbA1c in type 1 diabetic patients unsatisfactorily controlled by Multiple Daily Injections (MDI). Few trials have explored CSII for basal-bolus therapy in type 2 diabetes. Randomized Clinical Trials (RCTs) comparing CSII and MDI for at least 12 weeks in type 2 diabetic patients were retrieved, assessing between-group differences in HbA1c and insulin daily dose at endpoint, and incidence of hypoglycemia. A total of 4 RCTs was included in the analysis. CSII did not produce any significant improvement of HbA1c in comparison with MDI (Standardized difference in mean: 0.09(-0.08;0.26)%; p=0.31). No significant difference was observed in the rate of hypoglycemic episodes. CSII was associated with a nonsignificant trend toward the reduction of insulin doses used at the end of trial. Available data do not justify the use of CSII for basal-bolus insulin therapy in type 2 diabetes.

Comparison of insulin lispro with regular human insulin for the treatment of type 1 diabetes in adolescents

Background: Although insulin lispro (insulin LP) has been shown to improve post-prandial blood glucose (BG) control and reduce hypoglycemic episodes in adult patients with type 1 diabetes, there appear to have been few clinical studies focusing on its use in adolescents. Objective: This study compared the effects of insulin LP with those of regular human insulin (insulin R) on postprandial BG control and hypoglycemia in adolescents with type 1 diabetes. Methods: In this crossover, open-label study, adolescents between the ages of 9 and 18 years who had reached Tanner stage II puberty were randomized to receive either insulin LP immediately before meals or insulin R 30 to 45 minutes before meals, in addition to daily intermediate-acting insulin. After 4 months, patients were switched to the alternate treatment sequence. Eight-point BG profiles, hypoglycemia rate, and glycosylated hemoglobin (HbA 1c) were measured at baseline and end point. Results: Four hundred eighty-one adolescents participated in the study at 53 investigative sites in 15 countries; 463 were randomized to treatment (228 insulin LP, 235 insulin R), and 457 completed the study. Insulin LP given before breakfast resulted in significantly lower mean (±SD) 2-hour postprandial BG levels compared with insulin R (9.7 ± 4.0 mmol/L vs 10.6 ± 4.3 mmol/L, respectively; P < 0.001). Insulin LP given before dinner resulted in significantly lower 2-hour postprandial BG levels compared with insulin R (8.6 ± 3.5 mmol/L vs 9.3 ± 3.7 mmol/L; P = 0.003). No differences were seen between treatments in 2-hour postprandial BG levels after the midday meal. Mean baseline HbA 1c values were similar between sequence groups, and no between-group difference in HbA 1c was observed at end point (insulin LP, 8.69% ± 1.52%; insulin R, 8.70% ± 1.65%). Treatment with insulin LP resulted in a significantly lower incidence of hypoglycemic episodes per patient per 30 days compared with insulin R (4.02 ± 4.5 vs 4.37 ± 4.5, respectively; P = 0.023) and significantly fewer hypoglycemic episodes between midnight and 6 am (1.0 ± 1.9 vs 1.7 ± 2.6; P < 0.001). Conclusions: In adolescents with type 1 diabetes, insulin LP significantly improved postprandial glycemic control and reduced episodes of nocturnal hypoglycemia compared with insulin R. Insulin LP was well tolerated and effective as part of an intensified insulin regimen in this study population.