Glycaemic control and hypoglycaemia with insulin glargine 300U/mL versus insulin glargine 100U/mL in insulin-naïve people with type 2 diabetes: 12-month results from the EDITION 3 trial.

AIM: To explore if efficacy and safety findings for insulin glargine 300U/mL (Gla-300) versus insulin glargine 100U/mL (Gla-100), observed over 6 months in insulin-naïve people with type 2 diabetes, are maintained after 12 months. METHODS: EDITION 3 was a phase 3a, randomized, multicentre, open-label, parallel-group, treat-to-target study of once-daily Gla-300 versus Gla-100 (target fasting self-monitored plasma glucose, 4.4-5.6mmol/L [80-100mg/dL]). Participants completing the initial 6-month treatment phase continued their previously allocated basal insulin. RESULTS: Of 878 participants randomized, 337/439 (77%) and 314/439 (72%) assigned to Gla-300 and Gla-100, respectively, completed 12 months of treatment. Improved glycaemic control was sustained until 12 months in both treatment groups, with similar reductions in HbA1c from baseline to month 12 (difference: -0.08 [95% confidence interval (CI): -0.23 to 0.07] % or -0.9 [-2.5 to 0.8] mmol/mol). Relative risk of experiencing≥1 confirmed (≤3.9mmol/L [≤70mg/dL]) or severe hypoglycaemic event with Gla-300 versus Gla-100 was 0.86 (95% CI: 0.69 to 1.07) at night and 0.92 (0.82 to 1.03) at any time of day. For events with a glycaemic threshold of<3.0mmol/L (<54mg/dL) these numbers were 0.76 (0.49 to 1.19) and 0.66 (0.50 to 0.88). A similar pattern was seen for documented symptomatic events. No between-group differences in adverse events were identified. CONCLUSION: Over 12 months, Gla-300 treatment was as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes, with lower overall risk of hypoglycaemia at the<3.0mmol/L threshold.

Randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3.

AIMS: To compare the efficacy and safety of basal insulin peglispro (BIL), which has a flat pharmacokinetic and pharmacodynamic profile and a long duration of action, with insulin glargine (GL) in patients with type 1 diabetes. MATERIALS AND METHODS: In this phase III, 52-week, blinded study, we randomized 1114 adults with type 1 diabetes in a 3 : 2 distribution to receive either BIL (n = 664) or GL (n = 450) at bedtime, with preprandial insulin lispro, using intensive insulin management. The primary objective was to compare glycated haemoglobin (HbA1c) in the groups at 52 weeks, with a non-inferiority margin of 0.4%. RESULTS: At 52 weeks, mean (standard error) HbA1c was 7.38 (0.03)% with BIL and 7.61 (0.04)% with GL {difference -0.22% [95% confidence interval (CI) -0.32, -0.12]; p < 0.001}. At 52 weeks more BIL-treated patients reached HbA1c <7% (35% vs 26%; p < 0.001), the nocturnal hypoglycaemia rate was 47% lower (p < 0.001) and the total hypoglycaemia rate was 11% higher (p = 0.002) than in GL-treated patients, and there was no difference in severe hypoglycaemia rate. Patients receiving BIL lost weight, while those receiving GL gained weight [difference -1.8 kg (95% CI -2.3, -1.3); p < 0.001]. Treatment with BIL compared with GL at 52 weeks was associated with greater increases from baseline in levels of serum triglyceride [difference 0.19 mmol/l (95% CI 0.11, 0.26); p < 0.001] and alanine aminotransferase (ALT) levels [difference 6.5 IU/l (95% CI 4.1, 8.9), p < 0.001], and more frequent injection site reactions. CONCLUSIONS: In patients with type 1 diabetes, treatment with BIL compared with GL for 52 weeks resulted in a lower HbA1c, more patients with HbA1c levels <7%, and reduced nocturnal hypoglycaemia, but more total hypoglycaemia and injection site reactions and higher triglyceride and ALT levels.

Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12-month trial including 6-month extension.

AIMS: To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs (OADs). METHODS: EDITION 2 (NCT01499095) was a randomized, 6-month, multicentre, open-label, two-arm, phase IIIa study investigating once-daily Gla-300 versus Gla-100, plus OADs (excluding sulphonylureas), with a 6-month safety extension. RESULTS: Similar numbers of participants in each group completed 12 months of treatment [Gla-300, 315 participants (78%); Gla-100, 314 participants (77%)]. The reduction in glycated haemoglobin was maintained for 12 months with both treatments: least squares (LS) mean (standard error) change from baseline -0.55 (0.06)% for Gla-300 and -0.50 (0.06)% for Gla-100; LS mean difference -0.06 [95% confidence interval (CI) -0.22 to 0.10)%]. A significant relative reduction of 37% in the annualized rate of nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia was observed with Gla-300 compared with Gla-100: rate ratio 0.63 [(95% CI 0.42-0.96); p = 0.031], and fewer participants experienced ≥1 event [relative risk 0.84 (95% CI 0.71-0.99)]. Severe hypoglycaemia was infrequent. Weight gain was significantly lower with Gla-300 than Gla-100 [LS mean difference -0.7 (95% CI -1.3 to -0.2) kg; p = 0.009]. Both treatments were well tolerated with a similar pattern of adverse events (incidence of 69 and 60% in the Gla-300 and Gla-100 groups). CONCLUSIONS: In people with type 2 diabetes treated with Gla-300 or Gla-100, and non-sulphonylurea OADs, glycaemic control was sustained over 12 months, with less nocturnal hypoglycaemia in the Gla-300 group.

LEADER 2: baseline calcitonin in 9340 people with type 2 diabetes enrolled in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial: preliminary observations.

AIMS: To report preliminary data on baseline serum calcitonin concentrations and associated clinical characteristics in a global population with type 2 diabetes before liraglutide or placebo randomization. METHODS: The ongoing LEADER trial has enrolled 9340 people with type 2 diabetes and at high risk of cardiovascular disease at 410 centres worldwide. People with baseline serum calcitonin ≤ 50 ng/l were randomized to liraglutide once daily or placebo and will be followed for up to 5 years. Serum calcitonin was measured at baseline and will be measured annually thereafter. An independent committee of thyroid experts will oversee calcitonin monitoring throughout the trial and will review all calcitonin concentrations ≥ 20 ng/l. RESULTS: The mean age of participants was 64.3 ± 7.2 years, 64.3% were men, and mean the body mass index was 32.5 ± 6.3 kg/m(2). The median (interquartile range) baseline serum calcitonin values were 3.9 (1.0 to >7.6) ng/l in men and 1.0 (1.0 to >1) ng/l in women. Serum calcitonin was >10 ng/l in 14.6% of men and in 0.96% of women. In sex-specific multivariable linear analysis of covariance models, a reduced glomerular filtration rate (GFR) was associated with higher serum calcitonin concentrations that were statistically significant. A 20 ml/min/1.73 m(2) decrease in estimated GFR (eGFR) was associated with a 14% increase in serum calcitonin in women and an 11% increase in men. CONCLUSIONS: In the LEADER population, the prevalence of elevated serum calcitonin concentrations at baseline was high, and there was an inverse association between eGFR and serum calcitonin concentrations.

New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-lowering drugs: a randomized controlled trial (EDITION 3).

AIMS: To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of glargine 100 U/ml (Gla-100) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs. METHODS: The EDITION 3 study was a multicentre, open-label, parallel-group study. Participants were randomized to Gla-300 or Gla-100 once daily for 6 months, discontinuing sulphonylureas and glinides, with a dose titration aimed at achieving pre-breakfast plasma glucose concentrations of 4.4-5.6 mmol/l (80-100 mg/dl). The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to month 6. The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia from week 9 to month 6. Other measures of glycaemia and hypoglycaemia, weight change and insulin dose were assessed. RESULTS: Randomized participants (n = 878) had a mean (standard deviation) age of 57.7 (10.1) years, diabetes duration 9.8 (6.4) years, body mass index 33.0 (6.7) kg/m(2) and HbA1c 8.54 (1.06) % [69.8 (11.6) mmol/mol]. HbA1c levels decreased by equivalent amounts with the two treatments; the least squares mean difference in change from baseline was 0.04 [95% confidence interval (CI) -0.09 to 0.17] % or 0.4 (-1.0 to 1.9) mmol/mol. Numerically fewer participants reported ≥1 nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia from week 9 to month 6 [relative risk (RR) 0.89 (95% CI 0.66 to 1.20)] with Gla-300 versus Gla-100; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [RR 0.76 (95% CI 0.59 to 0.99)]. No between-treatment differences in adverse events were identified. CONCLUSIONS: Gla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes, with lower hypoglycaemia risk.

Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite similar improved glycaemic control in T1DM and T2DM.

AIMS: The basal insulin analogue LY2605541, a PEGylated insulin lispro with prolonged duration of action, was previously shown to be associated with modest weight loss in Phase 2, randomized, open-label trials in type 2 (N=288) and type 1 (N=137) diabetes mellitus (T2DM and T1DM), compared with modest weight gain with insulin glargine. Exploratory analyses were conducted to further characterize these findings. METHODS: Pearson correlations between change in body weight and other variables were calculated. Continuous variables were analysed using a mixed linear model with repeated measurements. Proportions of subjects with weight loss were analysed using Fisher's exact test for T2DM and Nagelkerke's method for T1DM. RESULTS: Weight loss was more common in LY2605541-treated patients than in patients treated with insulin glargine (T2DM: 56.9 vs. 40.2%, p=0.011; T1DM: 66.1 vs. 40.3%, p<0.001). More LY2605541-treated patients experienced ≥5% weight loss compared to patients treated with glargine (T2DM: 4.8 vs. 0%, p=0.033; T1DM: 11.9 vs. 0.8%, p<0.001). In both the T1DM and T2DM studies, weight change did not correlate with baseline body mass index (BMI), or change in HDL-cholesterol in either treatment group. No consistent correlations were found across both studies between weight change and any of the variables assessed; however, weight change was significantly correlated with hypoglycaemia rate in glargine-treated T2DM patients. CONCLUSION: In two Phase 2 trials, improved glycaemic control with long-acting basal insulin analogue LY2605541 is associated with weight loss in previously insulin-treated patients. This weight change is independent of baseline BMI or hypoglycaemia.

Exenatide once weekly improved glycaemic control, cardiometabolic risk factors and a composite index of an HbA1c < 7%, without weight gain or hypoglycaemia, over 52 weeks.

AIMS: Type 2 diabetes mellitus (T2DM) is often associated with cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia. The objective of this analysis was to evaluate potential effects of exenatide once weekly (ExQW), a GLP-1 receptor agonist, on glycaemic control and CV risk factors. METHODS: This analysis included 675 Intent-to-Treat patients with T2DM [baseline (mean ± SD) HbA1c, 8.1 ± 1.2%; fasting blood glucose (FBG), 166 ± 48 mg/dl; weight, 94.3 ± 19.4 kg; systolic/diastolic blood pressure (SBP/DBP), 129 ± 15/78 ± 9 mm Hg; total cholesterol, 178.5 ± 41.9 mg/dl; low-density lipoprotein (LDL), 100.1 ± 35.0 mg/dl; high-density lipoprotein (HDL), 44.5 ± 11.6 mg/dl; triglycerides, 155.6 ± 3.3 mg/dl; alanine aminotransferase (ALT), 32.1 ± 19.5 U/l] treated with diet and exercise alone or in combination with metformin, sulfonylurea, and/or thiazolidinedione who received 52 weeks of ExQW in four clinical trials. RESULTS: At 52 weeks, ExQW significantly improved HbA1c [mean (SE) change from baseline, -1.3 (0.05)%], FBG [-36.3 (2.02) mg/dl], body weight [-2.6 (0.19) kg], SBP/DBP [-3.6 (0.56) mm Hg/-1.2 (0.34) mm Hg], total cholesterol, -4.4 (1.33) mg/dl; LDL, -2.6 (1.08) mg/dl; HDL, 1.1 (0.31) mg/dl; triglycerides, -7 (1.6)%], and ALT [-4.3 (0.71) IU/l] concentrations, with greater improvements in patients with elevated analyte levels at baseline. Improvements were observed across a range of background antihyperglycaemia therapies. Of patients completing 52 weeks, 19% achieved the composite American Diabetes Association goal (HbA1c < 7.0%, BP < 130/80 mm Hg, LDL < 100 mg/dl), compared to 1% at baseline. Nearly half (48%) achieved HbA1c < 7.0% without weight gain or major/minor hypoglycaemia. Nausea was the most frequent adverse event and was predominantly mild. Hypoglycaemia was infrequent, and more common with a sulfonylurea. CONCLUSIONS: With 52 weeks of ExQW, patients experienced sustained improvements in glycaemic control and CV risk factors, with an increased likelihood of achieving both a clinically relevant composite outcome (HbA1c < 7% without weight gain or increased risk of hypoglycaemia) and a composite of key therapeutic goals (HbA1c < 7%, BP < 130/80 mm Hg, LDL < 100 mg/dl).

Metabolic outcomes of matched patient populations initiating exenatide BID vs. insulin glargine in an ambulatory care setting.

AIM: This observational study evaluated the clinical effectiveness of exenatide BID (exenatide) vs. insulin glargine (glargine) in patients with type 2 diabetes mellitus in ambulatory clinical practice. METHODS: Retrospective analyses were conducted using an electronic medical record (EMR) database among adult patients with type 2 diabetes mellitus initiating exenatide or glargine between 1 November 2006 and 30 April 2009. The cohorts were propensity-score matched to control baseline demographics, clinical measures, health status and medication use. The changes from baseline to a 12-month follow-up period for A1C (primary outcome), weight, body mass index (BMI), blood pressure and lipid levels were compared between the matched cohorts using paired tests. RESULTS: Propensity-score matching between the exenatide (n = 4494) and glargine (n = 5424) cohorts led to 2683 matched pairs with comparable characteristics, including age, gender and baseline clinical values. The exenatide cohort achieved a greater mean reduction in A1C (-0.6% vs. -0.4%, p < 0.01), weight (-2.6 kg vs. -0.2 kg, p < 0.01), BMI (-0.8 kg/m(2) vs. -0.04 kg/m(2) , p < 0.01) and systolic blood pressure (SBP) (-1.8 mmHg vs. -0.1 mmHg, p < 0.01) in the follow-up period. The changes in diastolic blood pressure and lipid levels were not significantly different between cohorts. CONCLUSIONS: Compared to glargine, exenatide-treated patients experienced significant reductions in A1C, weight, BMI and SBP. Acknowledging the limitations of observational research, exenatide showed greater clinical effectiveness than glargine from a large EMR database in the ambulatory care setting.

DURATION-2: efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once-weekly exenatide.

AIMS: In the initial 26-week, double-blind, double-dummy assessment period of the DURATION-2 trial in patients with Type 2 diabetes on metformin, the once-weekly glucagon-like peptide 1 (GLP-1) receptor agonist exenatide once-weekly resulted in greater HbA(1c) improvement and weight reduction compared with maximum approved daily doses of sitagliptin or pioglitazone. This subsequent, 26-week, open-label, uncontrolled assessment period evaluated the safety and efficacy of (i) continued exenatide once-weekly treatment and (ii) switching from sitagliptin or pioglitazone to exenatide once-weekly. METHODS: Randomised oral medications were discontinued and all patients received exenatide once-weekly. Of the 364 patients [original baseline HbA(1c) 8.5 ± 1.1% (70 mmol/mol), fasting plasma glucose 9.0 ± 2.5 mmol/l, weight 88 ± 20 kg) who continued into the open-label period, 319 patients (88%) completed 52 weeks. RESULTS: Evaluable patients who received only exenatide once-weekly demonstrated significant 52-week improvements (least square mean ± se) in HbA(1c) (-1.6 ± 0.1%), fasting plasma glucose (-1.8 ± 0.3 mmol/l) and weight (-1.8 ± 0.5 kg). Evaluable patients who switched from sitagliptin to exenatide once-weekly demonstrated significant incremental improvements in HbA(1c) (-0.3 ± 0.1%), fasting plasma glucose (-0.7 ± 0.2 mmol/l) and weight (-1.1 ± 0.3 kg). Patients who switched from pioglitazone to exenatide once-weekly maintained HbA(1c) and fasting plasma glucose improvements (week 52: -1.6 ± 0.1%, -1.7 ± 0.3 mmol/l), with significant weight reduction (-3.0 ± 0.3 kg). Exenatide once-weekly was generally well tolerated and adverse events were predominantly mild or moderate in intensity. Nausea was the most frequent adverse event in this assessment period (intent-to-treat: exenatide once-weekly-only 5%; sitagliptin→exenatide once-weekly 11%; pioglitazone→exenatide once-weekly 10%). No major hypoglycaemia was observed. CONCLUSIONS: Patients who switched to once-weekly exenatide from daily sitagliptin or pioglitazone had improved or sustained glycaemic control, with weight loss.

Long-term effect of rosiglitazone and/or ramipril on the incidence of diabetes.

AIMS/HYPOTHESIS: The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial reported that 3 years of therapy with rosiglitazone reduced the primary outcome of diabetes or death by 60%. Here we investigated whether an effect on diabetes prevention persists more than 1.5 years after therapy has been discontinued. METHODS: The DREAM On passive follow-up study was conducted at 49 of the 191 DREAM sites. Consenting participants were invited to have a repeat OGTT 1-2 years after active therapy ended. A diagnosis of diabetes at that time was based on either a fasting or 2 h plasma glucose level of ≥7.0 mmol/l or ≥11.1 mmol/l, respectively, or a confirmed diagnosis by a non-study physician. Regression to normoglycaemia was defined as a fasting and 2 h plasma glucose level of <6.1 mmol/l and <7.8 mmol/l, respectively. RESULTS: After a median of 1.6 years after the end of the trial and 4.3 years after randomisation, rosiglitazone participants had a 39% lower incidence of the primary outcome (hazard ratio [HR] 0.61, 95% CI 0.53-0.70; p < 0.0001) and 17% more regression to normoglycaemia (95% CI 1.01-1.34; p = 0.034). When the analysis was restricted to the passive follow-up period, a similar incidence of both the primary outcome and regression was observed in people from both treatment groups (HR 1.00, 95% CI 0.81-1.24 and HR 1.14, 95% CI 0.97-1.32, respectively). Similar effects were noted when new diabetes was analysed separately from death. Ramipril did not have any significant long-term effect. CONCLUSIONS/INTERPRETATION: Time-limited exposure to rosiglitazone reduces the longer term incidence of diabetes by delaying but not reversing the underlying disease process.

Long-term effect of rosiglitazone and/or ramipril on the incidence of diabetes: DREAM On (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication Ongoing Follow-up) Investigators

AIMS/HYPOTHESIS: The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial reported that 3 years of therapy with rosiglitazone reduced the primary outcome of diabetes or death by 60%. Here we investigated whether an effect on diabetes prevention persists more than 1.5 years after therapy has been discontinued. METHODS: The DREAM On passive follow-up study was conducted at 49 of the 191 DREAM sites. Consenting participants were invited to have a repeat OGTT 1-2 years after active therapy ended. A diagnosis of diabetes at that time was based on either a fasting or 2 h plasma glucose level of ¡Ý7.0 mmol/l or ¡Ý11.1 mmol/l, respectively, or a confirmed diagnosis by a non-study physician. Regression to normoglycaemia was defined as a fasting and 2 h plasma glucose level of <6.1 mmol/l and <7.8 mmol/l, respectively. RESULTS: After a median of 1.6 years after the end of the trial and 4.3 years after randomisation, rosiglitazone participants had a 39% lower incidence of the primary outcome (hazard ratio [HR] 0.61, 95% CI 0.53-0.70; p < 0.0001) and 17% more regression to normoglycaemia (95% CI 1.01-1.34; p = 0.034). When the analysis was restricted to the passive follow-up period, a similar incidence of both the primary outcome and regression was observed in people from both treatment groups (HR 1.00, 95% CI 0.81-1.24 and HR 1.14, 95% CI 0.97-1.32, respectively). Similar effects were noted when new diabetes was analysed separately from death. Ramipril did not have any significant long-term effect. CONCLUSIONS/INTERPRETATION: Time-limited exposure to rosiglitazone reduces the longer term incidence of diabetes by delaying but not reversing the underlying disease process.

Comparison of insulin analogue regimens in people with type 2 diabetes mellitus in the PREFER Study: a randomized controlled trial.

AIMS: Insulin analogues are widely used but few data exist comparing different analogue regimens. We compared two such regimens in type 2 diabetes mellitus (T2DM) uncontrolled by oral antidiabetic agents (OADs) with or without basal insulin. METHODS: In a 26-week multinational, multicentre, randomized treat-to-target trial, OADs were discontinued and subjects randomized to analogue basal-bolus therapy (insulin detemir once daily and insulin aspart mealtimes) or biphasic insulin aspart 30 (30% rapid-acting insulin aspart), twice daily. Insulin was titrated to targets for fasting, predinner and postprandial plasma glucose (PG), as appropriate. RESULTS: Of 719 subjects, 92% completed the study; 58% achieved haemoglobin fraction A(1c) (HbA(1c)) < or =7.0%, with reductions of 1.56% (to 6.96%) with basal-bolus therapy and 1.23% (to 7.17%) with biphasic insulin aspart. Reduction with basal-bolus therapy was superior in the overall population by 0.23% (p = 0.0052), with no difference between regimens in insulin-naive patients. Major hypoglycaemia occurred in five basal-bolus patients (0.9%) and in no patients with biphasic insulin aspart. Incidence of minor hypoglycaemia was similar in both groups. All insulin doses increased during titration, with increase in lunchtime insulin aspart dose and equal distribution of breakfast and dinner biphasic insulin aspart doses. Insulin detemir remained once daily in 87% of patients. CONCLUSIONS: Modern insulin analogue regimens, adjusted to PG targets, enable a majority of people with T2DM to reach HbA(1c)< or =7.0% after failure of OADs and OAD-basal insulin therapy. Insulin-treated patients may benefit more from transfer to analogue basal-bolus therapy, while insulin-naive individuals benefit equally well from the more convenient biphasic analogue regimen.

Characterizing blood pressure control in individuals with Type 2 diabetes: the relationship between clinic and self-monitored blood pressure.

AIMS: To determine the relationship between blood pressure (BP) measurement in the clinic and self-monitored blood pressure (SMBP); and to evaluate the accuracy of self-reported data in patients with Type 2 diabetes treated intensively for hypertension. METHODS: Seventy subjects had baseline and 1-week follow-up clinic BP measured using an Omron 907 automated device. During a contemporaneous 14-day period these subjects measured their BP at least four times each day using an Omron IC semiautomatic portable monitor which, unknown to them, contained an onboard memory capable of storing BP with corresponding time and date. RESULTS: There was no significant difference between mean clinic and mean self-monitored BP. Correlations between clinic BP and SMBP were r=0.61 (P<0.0001) for systolic BP and r=0.69 (P<0.0001) for diastolic BP. Clinic BP classified 56 subjects as uncontrolled hypertension (BP > or = 130/80 mmHg, adjusted for diabetes) and 14 subjects as controlled hypertension. Using World Health Organization-International Society of Hypertension criteria for SMBP (> or = 125/75 mmHg), 55 cases of clinic classified uncontrolled hypertension were confirmed, resulting in 98% sensitivity. Clinic and SMBP agreed in one case of controlled hypertension, resulting in 7% specificity. For all subjects, the median percent of values exceeding SMBP criteria for controlled hypertension was systolic 92% and diastolic 70%. Self-reporting precision averaged 89+/-10% (range 45-100%); under-reporting was 25+/-16% (ranging from 0 to 56%) and over-reporting was 12+/-15% (ranging from 0 to 46%). The overall logbook mean was not significantly different from the downloaded data from the Omron IC(R) monitors. CONCLUSIONS: SMBP was able to identify 13 patients with uncontrolled hypertension who, by clinic BP measurement, had been classified as controlled.

Comprehensive management of patients with type 2 diabetes: establishing priorities of care.

Type 2 diabetes is a complex metabolic disorder characterized by elevated blood glucose levels and a marked increase in the risk of cardiovascular disease (CVD). The increased CVD risk is caused by a unique cluster of metabolic abnormalities, including dyslipidemia, hypertension, insulin resistance, and hyperglycemia. To reduce the risk of cardiovascular complications in patients with type 2 diabetes, comprehensive management of risk factors is essential. Aggressive treatment of dyslipidemia and hypertension is known to benefit patients with type 2 diabetes. In addition, intensive glycemic control and targeted treatment of insulin resistance can further reduce the enormous burden of CVD in this high-risk population. Increasing evidence suggests that insulin resistance is one of the earliest markers of risk for both CVD and diabetes, and it is known that insulin resistance alone can significantly increase the risk of CVD. Type 2 diabetes and insulin resistance are both associated with disordered lipid metabolism, manifest in elevated triglyceride levels, low levels of high-density lipoprotein cholesterol, and small, dense low-density lipoprotein cholesterol particles. Patients with type 2 diabetes and insulin resistance have an increased risk of hypertension, which further contributes to their CVD risk. Each of these factors can also contribute to the risk of microvascular disease. To ensure that patients with type 2 diabetes receive comprehensive, high-quality care, specific standards have been developed. These standards can help providers establish clear treatment targets, identify specific priorities of care, and use therapies of known efficacy to reduce the risk of complications. This review summarizes the current standards of care for patients with type 2 diabetes, with an emphasis on treatments that reduce the cardiovascular risk factors. Using a case study approach, it reviews the essential components of diabetes care and proposes a rational approach to these complex cases--an approach that should result in consistent, high-quality care.

Use of an automated device for alternative site blood glucose monitoring.

OBJECTIVE: To evaluate the accuracy, comfort, and ease of use of a new automated device for blood glucose monitoring using the arm as an alternative sampling site. RESEARCH DESIGN AND METHODS: These studies use an automated hand-held device that applies a small vacuum, lances the skin, transfers blood onto an electrochemical test strip, and measures glucose. Patients who had type 1 or type 2 diabetes and had received no prior training using this device were recruited from five diabetes clinics. Testing was performed by the patients using this device and by trained healthcare professionals. Blood glucose was measured by 354 patients: from the arm using the device, from the finger using a laboratory reference instrument, and from the finger using the device via the secondary test port. Each patient completed a questionnaire rating the level of pain and ease of use of the device. RESULTS: Blood glucose results in samples obtained from the arm with the automated device agreed well with finger-stick plasma glucose results using a reference instrument (regression slope 0.98, intercept 0.01 mmol/l [0.1 mg/dl], r = 0.96). Error grid analysis showed that 100% of the measurements fell within zones A and B. In the survey, 60% of the patients reported that arm testing with the automated device was "painless;" another 31% of the patients stated that it was "much less painful," and 6% of patients considered using the device "less painful" than finger-stick testing. In a survey containing 15 questions for rating the ease of use with a scale of 1 to 6, the overall mean rating was 5.5. CONCLUSIONS: The automated device is easy to use and provides accurate glucose results; 97% of the patients found it less painful than finger-stick testing.

A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes.

OBJECTIVE: To determine the safety and efficacy of the long-acting insulin analog, insulin glargine, as a component of basal bolus therapy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro were randomized to receive insulin glargine (HOE 901), a long-acting basal insulin analog, once a day (n = 310) or NPH human insulin (n = 309) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study NPH insulin patients maintained their prior schedule of administration once or twice a day, whereas insulin glargine patients received basal insulin once a day at bedtime. RESULTS: Compared with all NPH insulin patients, insulin glargine patients had significant decreases in fasting blood glucose measured at home (means +/- SEM, -42.0 +/- 4.7 vs. -12.4 +/- 4.7 mg/dl [-2.33 +/- 0.26 vs. -0.69 +/- 0.26 mmol/l]; P = 0.0001). These differences were evident early and persisted throughout the study More patients in the insulin glargine group (29.6%) than in the NPH group (16.8%) reached a target fasting blood glucose of 119 mg/dl (< 6.6 mmol/l). However, there were no differences between the groups with respect to change in GHb. Insulin glargine treatment was also associated with a significant decrease in the variability of fasting blood glucose values (P = 0.0124). No differences in the occurrence of symptomatic hypoglycemia, including nocturnal hypoglycemia, were observed. Overall, adverse events were similar in the two treatment groups with the exception of injection site pain, which was more common in the insulin glargine group (6.1%) than in the NPH group (0.3%). Weight gain was 0.12 kg in insulin glargine patients and 0.54 kg in NPH insulin patients (P = 0.034). CONCLUSIONS: Basal insulin therapy with insulin glargine once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day in maintaining glycemic control in patients with type 1 diabetes receiving basal-bolus insulin treatment with insulin lispro.

Identifying variables associated with inaccurate self-monitoring of blood glucose: proposed guidelines to improve accuracy.

PURPOSE: This study was conducted to evaluate patients' proficiency in self-monitoring of blood glucose (SMBG). METHODS: Diabetes nurse educators in 4 suburban Minneapolis clinic sites surveyed the SMBG training/cure practices of 280 patients with type 1 and type 2 diabetes. Participant SMBG technique was measured by direct observation. Participants performed a finger puncture and used their own meters to measure the first blood sample. A second sample was measured on the HemoCue B Glucose analyzer, and a third sample was used to measure hemoglobin. The series of tests were then repeated. If either of the 2 glucose tests was more than 15% from the HemoCue value, participants were reeducated about the manufacturer's suggested procedure. RESULTS: Of the 280 participants, 19% had blood glucose test results greater than the 15% limit for meter accuracy. After reeducation, 69% of those who had initially failed achieved acceptable results. The most significant problems were lack of periodic meter technique evaluation, difficulty using wipe meters, incorrect use of control solutions, lack of hand washing even when observed, and unclean meters. CONCLUSIONS: As a result of the study, guidelines were subsequently developed to evaluate meter accuracy in an outpatient setting. Further effort is needed to establish standards for evaluating SMBG.

Optimization of insulin therapy in patients with type 2 diabetes.

OBJECTIVE: To analyze emerging trends in effective utilization of insulin in the treatment of type 2 diabetes. METHODS: A systematic management plan and requirements for successful insulin therapy in patients with type 2 diabetes are outlined. RESULTS: The key to successful management of type 2 diabetes with insulin therapy is the use of adequate amounts of insulin and a bolus-to-basal insulin ratio of 1:1. Patient education about the progressive nature of the disease and the importance of self-monitoring of blood glucose is essential. The most effective method of sustaining normal blood glucose levels is to mimic the physiologic response to intake of food and thereby control postprandial glycemic excursions. Rapid-acting insulin lispro is useful in this effort. In the development of effective insulin regimens, one option is use of an insulin sensitizer in combination with bedtime NPH insulin. CONCLUSION: Because of deteriorating beta cell function, insulin deficiency results and usually necessitates administration of exogenous insulin in patients with type 2 diabetes. The goal of insulin treatment of type 2 diabetes is to achieve near-normal glycemic control. The insulin secretory defect progresses over time; thus, therapy must be continually matched to the underlying pathophysiologic defects.