Absolute Change In HbA1c Research Articles

Hba1c Variability, Absolute Changes in Hba1c, and the Risk of Poor Glycemic Control among Older Adults with Diabetes Enrolled in Medicare Advantage Plans

Healthcare claims data for all diabetes patients aged 65 years or older and continuously enrolled in Medicare Advantage plans in Independence Blue Cross from 2013 to 2014 and had ≥ 3 HbA1c measurements in the 2013 measurement year (MY). We used patients’ zip codes to link to US census data to get socioeconomic status information. Poor glycemic control was identified as the most recent HbA1c level > 9.0% during the MY. HbA1c variability was defined as within-subject standard deviation of HbA1c levels; absolute change in HbA1c was defined as the difference between the most recent HbA1c level and the first HbA1c level measured in MY2013. Multivariable logistic regression models were created, with poor glycemic control in MY2014 as the outcome.

Effects of Long-Term Exercise Interventions on Glycaemic Control in Type 1 and Type 2 Diabetes: a Systematic Review.

Aim: Physical activity is one of the cornerstones in the prevention and management of diabetes mellitus, but the effects of different training forms on metabolic control still remain unclear. The aims of this review are to summarize the recommendations of 5 selected diabetes associations and to systematically review the effects of long-term supervised exercise interventions without calorie-restriction on glycemic control in people with type 1 and 2 diabetes focusing on resistance, endurance and combined training consisting of both endurance and resistance training. Methods: Literature searches were performed using MEDLINE for articles published between January 1, 2000 and March 17, 2015. Of 76 articles retrieved, 15 randomized and controlled studies met the inclusion criteria and allowed for examining the effect of exercise training in type 1 and 2 diabetes. Results: Diabetes associations recommend volume-focused exercise in their guidelines. In our analysis, all 3 training forms have the potential to improve the glycemic control, as assessed by HbA1c (absolute changes in HbA1c ranging from -0.1% to -1.1% (-1.1 to -12 mmol/mol) in resistance training, from -0.2% to -1.6% (-2.2 to -17.5 mmol/mol) in endurance training and from +0.1% to -1.5% (+1.1 to -16.4 mmol/mol) in combined training, respectively). Conclusions: There is evidence that combined exercise training may improve glycemic control to a greater extent than single forms of exercise, especially under moderate-intensive training conditions with equal training durations. In addition, intensity of training appears to be an important determinant of the degree of metabolic improvement. Nonetheless, it is still unknown to what extent exercise effects glycemic homeostasis.

Relationship of HbA1c variability, absolute changes in HbA1c, and all-cause mortality in type 2 diabetes: a Danish population-based prospective observational study

ObjectiveWe assessed the relationship of mortality with glycated hemoglobin (HbA1c) variability and with absolute change in HbA1c.DesignA population-based prospective observational study with a median follow-up time of 6 years.MethodsBased on...

PRM203 - Modeling the Effect of Combining Alogliptin With Dual therapy in Type 2 Diabetes

To estimate the impact of combining the dipeptidyl peptidase-4 (DPP-4) inhibitor, alogliptin, with metformin and sulfonylurea (alogliptin triple therapy) to achieve glycemic control in patients with type 2 diabetes. Since no clinical trial of alogliptin triple therapy has been conducted, the effect of adding alogliptin to dual therapy (metformin+sulfonylurea) was modeled using novel additive effect methodology, utilizing data from a previous mixed treatment comparison (MTC). The following assumptions were made: the efficacy of triple therapy can be estimated as a function of its constituent parts, and the efficacies of the constituent parts are equivalent. Pooled data for the absolute change from baseline in glycosylated hemoglobin (HbA1c) from trials of sitagliptin, linagliptin, and vildagliptin triple therapy, and for their constituent parts, informed the model. A weighting factor, β coefficient, derived from DPP-4 mono, dual, and triple therapy trials, was used to estimate the effect size for triple therapy using the sum of the constituent parts. The estimated mean β value was validated against the observed effect size of alogliptin+pioglitazone+metformin, using the pooled effect from the MTC. An estimated mean β coefficient value of 0.83 represented the DPP-4 inhibitor class. Validation of the approach resulted in a similar β coefficient for pioglitazone triple therapy (0.82). Absolute change in HbA1c from baseline for alogliptin triple therapy was estimated as -0.77% (95% CI -1.16, -0.39). Similar values were observed in the MTC for sitagliptin -0.94% (95% CI -7.34,5. 40), linagliptin -0.65 (95% CI -6.87,5. 60), and vildagliptin -0.80% (95% CI -7.00,5. 43). The wide confidence interval is consistent with expectations in the literature and is a limitation of the method employed, in that it requires the variance of the individual studies to be summated. Nevertheless, the method demonstrates the value of modeling when clinical trial evidence is not available.

Effectiveness of general practice based, practice nurse led telephone coaching on glycaemic control of type 2 diabetes: the Patient Engagement And Coaching for Health (PEACH) pragmatic cluster randomised controlled trial

Objective To evaluate the effectiveness of goal focused telephone coaching by practice nurses in improving glycaemic control in patients with type 2 diabetes in Australia.Design Prospective, cluster randomised controlled trial,...

Diabetes Is the Main Factor Accounting for Hypomagnesemia in Obese Subjects

ObjectiveType 2 diabetes (T2DM) and obesity are associated with magnesium deficiency. We aimed to determine whether the presence of type 2 diabetes and the degree of metabolic control are related to low serum magnesium levels in obese individuals.MethodsA) Case-control study: 200 obese subjects [50 with T2DM (cases) and 150 without diabetes (controls)] prospectively recruited. B) Interventional study: the effect of bariatric surgery on serum magnesium levels was examined in a subset of 120 obese subjects (40 with type 2 diabetes and 80 without diabetes).ResultsType 2 diabetic patients showed lower serum magnesium levels [0.75±0.07 vs. 0.81±0.06 mmol/L; mean difference −0.06 (95% CI −0.09 to −0.04); p<0.001] than non-diabetic patients. Forty-eight percent of diabetic subjects, but only 15% of non-diabetic subjects showed a serum magnesium concentration lower than 0.75 mmol/L. Significant negative correlations between magnesium and fasting plasma glucose, HbA1c, HOMA-IR, and BMI were detected. Multiple linear regression analysis showed that fasting plasma glucose and HbA1c independently predicted serum magnesium. After bariatric surgery serum magnesium increased only in those patients in whom diabetes was resolved, but remain unchanged in those who not, without difference in loss weight between groups. Changes in serum magnesium negatively correlated with changes in fasting plasma glucose and HbA1c. Absolute changes in HbA1c independently predicted magnesium changes in the multiple linear regression analysis.ConclusionsOur results provide evidence that the presence of diabetes and the degree of metabolic control are essential in accounting for the lower levels of magnesium that exist in obese subjects.

Saxagliptin improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus and renal impairment

To evaluate the efficacy and safety of saxagliptin vs. placebo in patients with type 2 diabetes mellitus (T2DM) and renal impairment. In this multicentre, randomized, parallel-group, double-blind, placebo-controlled study, patients with glycated haemoglobin (HbA1c) 7-11% and creatinine clearance <50 ml/min were stratified by baseline renal impairment (moderate, severe or end-stage on haemodialysis), and randomized (1 : 1) to saxagliptin 2.5 mg once daily or placebo for 12 weeks. Oral antihyperglycaemic drugs and insulin therapy present at enrolment were continued throughout the study. The absolute change in HbA1c from baseline to week 12 (primary efficacy end-point) was analysed using an analysis of covariance model with last observation carried forward methodology. A total of 170 patients were randomized and treated. The adjusted mean decrease from baseline to week 12 in HbA1c was statistically significantly greater in the saxagliptin group than in the placebo group; the difference between treatments was -0.42% (95% confidence interval: -0.71 to -0.12%, p = 0.007). Adjusted mean HbA1c decreases from baseline to week 12 were numerically greater with saxagliptin than with placebo in the subgroups of patients with moderate (-0.64 vs. -0.05%) and severe (-0.95 vs. -0.50%) renal impairment. HbA1c reductions were similar between saxagliptin and placebo in the subgroup with end-stage renal disease on haemodialysis (-0.84 vs. -0.87%). Saxagliptin was generally well tolerated; incidences of adverse events and hypoglycaemic events were similar to placebo. Saxagliptin 2.5 mg once daily is a well-tolerated treatment option for patients with inadequately controlled T2DM and renal impairment.

Relationship of baseline HbA1c, HbA1c change and HbA1c target of &lt; 7% with insulin analogues in type 2 diabetes: a meta-analysis of randomised controlled trials

We performed a meta-analysis of randomised controlled trials (RCTs) with insulin analogues in type 2 diabetes utilising a least-squared regression model in order to assess the relationship between baseline HbA1c, the magnitude of HbA1c decrease and attainment of HbA1c target of < 7%. Randomised controlled trials involving insulin regimens (basal, prandial, biphasic and basal-bolus) were identified through electronic searches (MEDLINE, EMBASE, CINAHL and The Cochrane Library) through September 2010. We included any study arm of RCTs if they were at least 12 weeks in duration; the number of patients in any arm was more than 30 and reported the baseline HbA1c and change from baseline HbA1c. We found 87 studies, with a total of 135 arms, and 38,803 patients. The weighted R(2) values for the overall analysis assessing the association between baseline HbA1c and absolute change in HbA1c or the proportion of patients at target were 0.485 (p < 0.001) and 0.146 (p < 0.001), respectively. Subanalyses of insulin regimens for the association between basal HbA1c and absolute decrease of HbA1c produced weighted R(2), which were significant for all insulin regimens with the highest association for basal-bolus (R(2) = 0.719, p < 0.001). The strong positive relationship between baseline HbA1c and the magnitude of HbA1c change we found in RCTs using insulin analogues in type 2 diabetes should be considered when assessing the clinical efficacy of insulin therapies.

PS1-10: Response to Metformin and Genetic Variants of Organic Cation and Multidrug and Toxin Extrusion Transporters

Background and Aims: Metformin is the most widely-used anti-diabetic drug in the United States. However, medication management fails to achieve therapeutic goals in ~20% of patients. This study attempted to identify genetic polymorphisms associated with metformin treatment failure. We studied the associations between polymorphisms in two liver and kidney organic cation transporter genes (OCT1 & OCT2) and two kidney multidrug and toxin extrusion transporter genes, (MATE1 & MATE2K) and response to metformin monotherapy. Methods: At Kaiser Permanente Southeast and Marshfield Clinic Research Foundation we identified 304 type 2 diabetes (T2DM) patients on metformin monotherapy who: were enrolled for >=6 months prior to initiation; remained on metformin >= 90 days following initiation; and had a HgbA1c measured prior to first metformin prescription and then after initiation. From this group we selected 171 patients who had not received metformin or other anti-diabetics previously, and had baseline HbA1c levels >7.0% prior to metformin initiation. We genotyped 10 SNPs, and assessed response by measuring absolute and relative change in HbA1c after after metformin initiation. Results: Three SNPs were identified that were significantly associated with reduced response to metformin, after adjustment for baseline HbA1c, dose, and ethnicity. In a dominant model, heterozygosity or homozygosity for minor A allele in the MATE1 intronic SNP, rs2289669, resulted in a smaller absolute change in HbA1c (mean of 0.45% less reduction in absolute change in HbA1c; 95% CI 0.17 to 0.74%) compared to individuals homozygous for major G allele. In a recessive model, homozygosity for minor A allele in MATE2K 5′-UTR SNP, rs12943590, resulted in smaller absolute change in HbA1c (mean of 0.43% less reduction in absolute change in HbA1c, 95% CI 0.053 to 0.86%). The reduced function SNPs in OCT1 & OCT2 were not associated with metformin response, except for rs34059508 (G465R). This SNP showed a positive (but not statistically significant) association with smaller absolute change in HbA1c (mean of 0.49%; 95% CI −0.06354 to 1.045%). Conclusions: These three variants of metformin transporter genes may be important for personalizing treatment for patients with T2DM. A replication study in a larger population is currently being planned.

Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12‐week, double‐blind, randomized, placebo‐controlled, multicentre trial

To determine efficacy and tolerability of dutogliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, in patients with type 2 diabetes mellitus. This was a 12-week, multicentre, randomized, double-blind, placebo-controlled trial in 423 patients with type 2 diabetes with suboptimal metabolic control. Following a 2-week single-blind placebo run-in, patients aged 18-75 years with a body mass index of 25-48 kg/m(2) and baseline HbA1c of 7.3-11.0% were randomized 2:2:1 to receive once-daily oral therapy with either dutogliptin (400 or 200 mg) or placebo on a background medication of either metformin alone, a thiazolidinedione (TZD) alone or a combination of metformin plus a TZD. Average HbA1c at baseline was 8.4%. Administration of dutogliptin 400 and 200 mg for 12 weeks decreased HbA1c by -0.52% (p < 0.001) and -0.35% (p = 0.006), respectively (placebo-corrected values), with absolute changes in HbA1c for the 400 mg, 200 mg and placebo groups of -0.82, -0.64 and -0.3%, respectively. The proportion of patients achieving an HbA1c < 7% was 27, 21 and 12% at dutogliptin doses of 400 and 200 mg or placebo, respectively (p = 0.008 for comparison of 400 mg vs. placebo). Fasting plasma glucose (FPG) levels were significantly reduced in both active treatment groups compared to placebo: the placebo-corrected difference was -1.00 mmol/l (p < 0.001) for the 400 mg group and -0.88 mmol/l (p = 0.003) for the 200 mg group. Dutogliptin caused significantly greater reductions in postprandial glucose AUC (0-2h) in both the 400 and 200 mg groups (placebo corrected values -2.58 mmol/l/h, p < 0.001 and -1.63 mmol/l/h, p = 0.032, respectively). In general, patients tolerated the study drug well. There were minor, not clinically meaningful differences in adverse events (AEs) between dutogliptin-treated patients and placebo controls, and 60% of all reported AEs were mild. Vital signs and body weight were stable, and routine safety laboratory parameters did not change compared with placebo. Trough ex vivo DPP4 inhibition at the end of the 12-week treatment period was 80 and 70%, at the 400 and 200 mg doses of dutogliptin, respectively. Dutogliptin treatment for 12 weeks improved glycaemic control in patients with type 2 diabetes who were on a background medication of metformin, a TZD or metformin plus a TZD. Tolerability was favourable for both doses tested. The 400 mg dose of dutogliptin resulted in larger changes of HbA1c and FPG and more subjects reached an HbA1c target of < 7% than the 200 mg dose.

Relationship of Baseline HbA1c and Efficacy of Current Glucose Lowering Therapies: A Meta-Analysis of Randomised Clinical Trials

Diabet. Med. 27, 309–317 (2010) Abstract Aims Baseline glycated haemoglobin (HbA1c) concentrations vary between clinical trials of glucose-lowering agents and this may affect interpretation of clinical efficacy. The objective of this study is to quantify the relationship between baseline HbA1c and reduction of HbA1c in clinical trials. Methods PubMed literature searches from 1991 to 2007. Randomized controlled studies with placebo-controlled or comparator arms [≥ 9 patients in the intent-to-treat (ITT) population] ranging in duration from 23 to 52 weeks, in which baseline and change in glycated haemoglobin (HbA1c) were reported. The relationship between baseline HbA1c and change in HbA1c was analysed by a weighted least-squared regression model accounting for ITT population and variance of HbA1c change. Fourteen per cent of independently abstracted studies met the selection criteria. Results Meta-analysis from 59 clinical trials (8479 patients) produced weighted R2 of 0.35 (P < 0.0001) for the association of baseline HbA1c and absolute change in HbA1c. Subanalysis of eight metformin clinical trials demonstrated a stronger association [weighted R2 of 0.67 (P = 0.0130)]. Exclusion of metformin clinical trials from the overall meta-analysis (n = 51) yielded a weighted R2 of 0.31 (P < 0.0001). Subanalyses of clinical trials of glucose-lowering therapies predominantly targeting fasting (n = 37) or postprandial (n = 22) blood glucose produced weighted R2 values of 0.27 (P < 0.001) and 0.42 (P < 0.005), respectively. Conclusions These data demonstrate a positive relationship between baseline HbA1c and the magnitude of HbA1c change across 10 categories of glucose-lowering therapies, irrespective of class or mode of action. These observations should be considered when assessing clinical efficacy of diabetes therapies derived from clinical trials.

Inhaled dry powder insulin for the treatment of diabetes mellitus

Background:Inhaled dry powder insulin (IDPI) is the first inhaled insulin approved for the treatment of type 1 and type 2 diabetes mellitus (DM). Objective:This article reviews available information on IDPI, focusing on its clinical pharmacokinetics, comparative efficacy, tolerability, adverse events, dosage and administration, and cost. Methods:MEDLINE (1966–July 2006) and Web of Science (1995–July 2006) were searched for original research and review articles published in English. The search terms used were inhaled insulin, inhaled human insulin, rDNA origin inhalation powder, inbaled dry powder insulin, and IDPI. All published comparative efficacy studies were included in the review, as well as selected information from the package insert for IDPI. Results:IDPI is an inhaled dry powder form of regular human insulin (RHI) that is used as a premeal insulin to improve glycemic control by reducing postprandial glucose excursions. The literature search identified 5 efficacy trials comparing reductions in glycosylated hemoglobin (HbA1c) in a total of 582 patients with type 1 DM who received either premeal IDPI plus neutral protamine Hagedorn (NPH) or Ultralente insulin or injectable RHI plus NPH or Ultralente insulin. The search identified 5 comparative efficacy studies of IDPI monotherapy or the addition of IDPI to the current regimen in a total of 1413 patients with type 2 DM that was uncontrolled with diet and exercise, metformin, a sulfonylurea, metformin and a sulfonylurea, or a secretagogue plus an insulin sensitizer. The use of IDPI as a mealtime insulin in these studies was associated with absolute changes in HbA1c ranging from −0.6% to +0.1% in patients with type 1 DM and from −1.4% to −2.9% in patients with type 2 DM. HbA1c values <7% were achieved in 16.9% to 28.2% of patients with type 1 DM and 16.7% to 44.0% of patients with type 2 DM. The most common nonrespiratory adverse event noted during clinical trials of IDPI was hypoglycemia (type 1 DM: 8.6–9.3 episodes/subject-month; type 2 DM: 0.3–1.4 episodes/subject-month), and the most common adverse event involving the pulmonary system was cough (21.9%–29.5%). Conclusions:IDPI is the first available inhaled insulin. It provides an additional option for the achievement of HbA1c goals with a premeal insulin.

Starting Insulin Therapy in Type 2 Diabetes: Twice-Daily Biphasic Insulin Aspart 30 Plus Metformin versus Once-Daily Insulin Glargine Plus Glimepiride

To compare the efficacy and safety of two analog insulins as starting regimens in insulin-naïve Type 2 diabetes patients. In this randomized, open-label parallel study, twice-daily biphasic insulin aspart 30 (30% soluble and 70% protaminated insulin aspart; BIAsp 30) plus metformin (met) was compared with once-daily insulin glargine (glarg) plus glimepiride (glim) in 255 insulin-naïve patients (131 male; mean+/-SD age, 61.2+/-9.1 years). Mean baseline HbA (1c) (+/-SD) was 9.2+/-1.4% and 8.9+/-1.3% for BIAsp 30 plus met ( N=128) and glarg plus glim ( N=127), respectively ( P=0.0747). Primary endpoint was the difference in absolute change in HbA (1c) between groups after 26 weeks of treatment. HbA (1c) change was significantly greater in the BIAsp 30 plus met group than the glarg plus glim group (between-group difference: -0.5% (95% CI: -0.8; -0.2); P=0.0002). Mean prandial plasma glucose increment was significantly lower for BIAsp 30 plus met compared with glarg plus glim: 1.4+/-1.4 mmol/l vs. 2.2+/-1.8 mmol/l; P=0.0002. During the maintenance phase (weeks 6-26), one major hypoglycemic episode occurred in each group; 20.3% and 9% of patients experienced minor hypoglycemic episodes in the BIAsp 30 plus met and glarg plus glim groups, respectively ( P=0.0124). At end-of-trial, mean daily insulin doses were 0.40 U/kg BIAsp 30 and 0.39 U/kg glarg. Glarg plus glim-treated patients experienced significant weight gain of 1.5 kg (95% CI: 0.84; 2.19; P<0.0001). Weight change with BIAsp 30 plus met of +0.7 kg was not statistically significant (95% CI: -0.07; 1.42; P=0.0762). Starting insulin in Type 2 diabetes patients with twice-daily BIAsp 30 plus met can reduce HbA (1c) and mean prandial plasma glucose increment to a greater extent than once-daily glarg plus glim.