Understanding Prediabetes in a Medicare Advantage Population Using Data Adaptive Techniques.

The objective was to identify individuals with undiagnosed prediabetes from administrative data using adaptive techniques. The data source was a national Medicare Advantage Prescription Drug (MAPD) plan administrative data set. A retrospective, cross-sectional study developed and evaluated data adaptive logistic regression, decision tree, neural network, and ensemble predictive models for metabolic syndrome and prediabetes using 3 mutually exclusive cohorts (N = 279,903). The misclassification rate (MCR), average squared error (ASE), c-statistics, sensitivity (SN), and false positive (FP) rates were compared to select the final predictive models. MAPD individuals with continuous enrollment from 2013 to 2014 were included. Metabolic syndrome and prediabetes were defined using clinical guidelines, diagnosis, and laboratory data. A total of 512 variables identified through subject matter expertise in addition to utilizing all data available were evaluated for the modeling. The ensemble model demonstrated better discrimination (c-statistics, MCR, and ASE of 0.83, 0.24, and 0.16, respectively), high SN, and low FP rate in predicting metabolic syndrome than the individual data adaptive modeling techniques. Logistic regression demonstrated better discrimination (c-statistics, MCR, and ASE of 0.67, 0.13, and 0.11 respectively), high SN, and low FP rate in predicting prediabetes than the other adaptive modeling techniques or ensemble methods. The scored data predicted prediabetes in 44% of the MAPD population, which is comparable to 2005-2006 National Health and Nutrition Examination Survey prediabetes rates of 41%. The logistic regression model demonstrated good performance in predicting undiagnosed prediabetes in MAPD individuals.

Predictors of all-cause 30 day readmission among Medicare patients with type 2 diabetes.

OBJECTIVE: Readmission is costly among patients with type 2 diabetes (T2DM) in Medicare Advantage Prescription Drug Plans; identifying high-risk patients is necessary for targeting reduction programs. The objective of this study was to develop a claims-based algorithm to predict all-cause 30 day readmission among patients with T2DM. METHODS: This study used administrative data from 1 January 2012 through 31 January 2014. The cohort included hospitalized T2DM patients, aged 18-90 with ≥12 months' continuous enrollment before an unplanned hospital admission and ≥1 month of enrollment post-discharge, excluding patients in long-term care >30 days pre-index. Multivariate logistic regression predicted the likelihood of readmission following hospitalization in 2013. The analytic file was randomly split into training and test datasets to build and validate the model. Candidate variables included physician and patient demographics, baseline clinical conditions, and healthcare utilization metrics. Clinical conditions were classified using the Healthcare Cost and Utilization Project clinical classification system for ICD-9-CM. RESULTS: Of 63,237 individuals, 17.1% experienced a readmission. Of nearly 200 candidate variables, 14 were predictors of readmission, including total cumulative number of days for inpatient stays and the number of emergency department visits in the baseline period. Male gender, older age, and certain comorbidities were associated with higher likelihood of readmission. The final model demonstrated good discriminant ability (c-statistic = 0.82). CONCLUSIONS: This study provided evidence that certain patient characteristics and healthcare utilization are predictive of readmission. An algorithm with good discriminant ability was developed which could be used to target readmission reduction programs. Physician gender, specialty, and ownership status did not appear to influence the likelihood of readmission.

A Historical Retrospective Analysis of the Impact of Diabetes Quality Measure Attainment on Outcomes in Medicare Advantage Members.

The objective of this study was to assess achievement of 4 diabetes mellitus (DM)-related quality measures (QMs) and examine the relationship between QM attainment, concurrent health care costs, and DM complications over 1 year by conducting a retrospective analysis of claims data for Medicare Advantage Prescription Drug plan members with DM. Claims and member-level quality data were used to assess QM achievement, concurrent health care costs, and presence of new or worsening DM complications during the QM year. Multivariable regression models were used to examine the relationship between QM achievement and outcome measures controlling for potentially confounding baseline characteristics. QM attainment rates ranged from 54.2% for DM Treatment measure to 83.4% for Cholesterol Screening measure. Odds of new or worsening complications were greater for members who did not meet the Blood Sugar Controlled performance goal (odds ratio [OR]: 1.12, P < 0.001), DM Treatment goal (OR: 1.40, P < 0.001), or Cholesterol Screening goal (OR: 1.32, P < 0.001). Failure to attain the DM Medication Adherence goal was associated with lower odds of new or worsening complications (OR: 0.94, P < 0.001). In the regression models, all-cause health care costs were greater for members who achieved the Blood Sugar Controlled quality goal (P < 0.001), but lower for members who attained DM Treatment (P < 0.001) and low-density lipoprotein Cholesterol Screening goals (P < 0.001). There was no statistically significant relationship between attaining the DM Medication Adherence measure and all-cause costs. Achievement rates for individual QMs varied across the study population and relationships between QM attainment, health care costs, and DM complications during the QM measurement year were mixed.

Early treatment revisions by addition or switch for type 2 diabetes: impact on glycemic control, diabetic complications, and healthcare costs.

BACKGROUND: The study examined the prevalence of early treatment revisions after glycosylated hemoglobin (HbA1c) ≥9.0% (75 mmol/mol) and estimated the impact of early treatment revisions on glycemic control, diabetic complications, and costs. RESEARCH DESIGN AND METHODS: A retrospective cohort study of administrative claims data of plan members with type 2 diabetes and HbA1c ≥9.0% (75 mmol/mol) was completed. Treatment revision was identified as treatment addition or switch. Glycemic control was measured as HbA1c during 6-12 months following the first qualifying HbA1c ≥9.0% (75 mmol/mol) laboratory result. Complications severity (via Diabetes Complication Severity Index (DCSI)) and costs were measured after 12, 24, and 36 months. Unadjusted comparisons and multivariable models were used to examine the relationship between early treatment revision (within 90 days of HbA1c) and outcomes after controlling for potentially confounding factors measured during a 12-month baseline period. RESULTS: 8463 participants were included with a mean baseline HbA1c of 10.2% (75 mmol/mol). Early treatment revision was associated with greater reduction in HbA1c at 6-12 months (-2.10% vs -1.87%; p<0.001). No significant relationship was observed between early treatment revision and DCSI at 12, 24, or 36 months (p=0.931, p=0.332, and p=0.418). Total costs, medical costs, and pharmacy costs at 12, 24, or 36 months were greater for the early treatment revision group compared with the delayed treatment revision group (all p<0.05). CONCLUSIONS: The findings suggest that in patients with type 2 diabetes mellitus, treatment revision within 90 days of finding an HbA1c ≥9.0% is associated with a greater level of near-term glycemic control and higher cost. The impact on end points such as diabetic complications may not be realized over relatively short time frames.

Type 2 Diabetes Mellitus Patients' Healthcare Costs Related to Inpatient Hospitalizations: A Retrospective Administrative Claims Database Study.

INTRODUCTION: Diabetes-related healthcare costs are increasing in the United States, with inpatient hospitalization the largest component of medical expenditures. The aims of this study were to characterize hospitalized type 2 diabetes mellitus (T2DM) patients, understand the relationship between hospitalization and healthcare costs, and explore treatment modification after inpatient hospitalization. METHODS: A retrospective cohort analysis of Humana Medicare Advantage and commercial members with T2DM was conducted. T2DM members were identified and assigned to three groups: (1) inpatient hospitalization (IPH) without a 30-day readmit (IPH group); (2) IPH with a 30-day readmission (IPH readmission group); and, (3) matched non-IPH group. Demographics, clinical characteristics, comorbidities and healthcare costs were measured based on enrollment data and claims. Descriptive statistics were used and the relationship between IPH and costs was assessed using generalized linear models. RESULTS: A total of 15,555 IPH patients, 1757 IPH readmission patients, and 17,312 matched non-IPH patients were included in the study. The IPH readmission group had the highest adjusted mean all-cause total costs ($76,806), followed by the IPH group ($42,011), and the non-IPH group ($9624). A similar trend was observed for adjusted all-cause mean medical and pharmacy costs. DM-related total healthcare costs were highest for the IPH readmission group ($13,714), followed by the IPH group ($7477), and non-IPH group ($1620). While overall therapy modification (discontinuation, addition, switch) was low, T2DM patients with an IPH (with or without a readmission) had greater rates of therapy modification relative to the non-IPH patients. CONCLUSION: Adjusted all-cause and DM-related total costs were greatest for IPH readmission patients. Rates of treatment modification within 10 days of discharge after IPH were generally low. Identifying T2DM patients at high risk of readmission and employing methods to decrease that risk during the index hospitalization could have a significant impact on health system costs. FUNDING: Novo Nordisk.

Long-term safety and tolerability of saxagliptin add-on therapy in older patients (aged ≥ 65 years) with type 2 diabetes.

BACKGROUND: Treatment decisions for older patients with type 2 diabetes mellitus must balance glycemic control and adverse event risk. The objective of this study was to evaluate the long-term safety and tolerability of saxagliptin 5 mg as add-on therapy to common antihyperglycemic drugs in patients aged ≥ 65 years and <65 years. METHODS: Pooled adverse event data from three placebo-controlled trials of 76-206 weeks' duration in older (≥ 65 years) and younger (<65 years) patients receiving saxagliptin 5 mg or matching placebo added to metformin, glyburide, or a thiazolidinedione were analyzed. Measurements were calculated from day of first dose to specified event or last dose and included time at risk for adverse events, treatment-related adverse events, serious adverse events, adverse events leading to discontinuation, and events of special interest. Weighted incidence rates (number of events/total time) and incidence rate ratios (saxagliptin/placebo) with 95% confidence intervals were calculated (Mantel-Haenszel test). RESULTS: A total of 205 older (mean age 69 years; saxagliptin, n=99; placebo, n=106) and 1,055 younger (mean age 52 years; saxagliptin, n=531; placebo, n=524) patients were assessed. Regardless of age category, the adverse event incidence rates were generally similar between treatments, with confidence intervals for incidence rate ratios bridging 1. Treatment-related adverse events occurred in 36 older patients receiving saxagliptin versus 32 receiving placebo (incidence rate 34.1 versus 27.1 per 100 person-years) and in 150 younger patients in both treatment groups (incidence rate 24.0 versus 27.8 per 100 person-years). With saxagliptin versus placebo, serious adverse events occurred in eight versus 14 older (incidence rate 5.7 versus 9.9 per 100 person-years) and 49 versus 44 younger patients (incidence rate 6.5 versus 6.6 per 100 person-years). There were two deaths (one patient ≥ 65 years) with saxagliptin and six (none aged ≥ 65 years) with placebo. Older patients rarely experienced symptomatic confirmed hypoglycemia (fingerstick glucose ≤ 50 mg/dL; saxagliptin, n=1; placebo, n=2). CONCLUSION: Saxagliptin add-on therapy was generally well tolerated in older patients aged ≥ 65 years with type 2 diabetes mellitus, with a long-term safety profile similar to that of placebo.

Saxagliptin efficacy and safety in patients with type 2 diabetes receiving concomitant statin therapy.

AIMS: To examine whether concomitant statin therapy affects glycemic control with saxagliptin 2.5 and 5mg/d in patients with type 2 diabetes mellitus (T2DM). METHODS: Efficacy and safety were analyzed post hoc for pooled data from 9 saxagliptin randomized, placebo-controlled trials with a primary 24-week treatment period (4 monotherapy, 2 add-on to metformin, 1 each add-on to a sulfonylurea, thiazolidinedione, or insulin±metformin). Safety was also assessed in an 11-study, 24-week pool and an extended 20-study pool, which included 9 additional 4- to 52-week randomized studies. Comparisons were performed for patient groups defined by baseline statin use. RESULTS: Saxagliptin produced greater mean reductions in glycated hemoglobin than placebo, with no interaction between treatment and baseline statin use (P=0.47). In patients receiving saxagliptin 2.5 and 5mg and placebo, the proportion of patients with ≥1 adverse event (AE) was 78.1%, 64.0%, and 63.2%, respectively, in patients with any statin use and 70.6%, 57.9%, and 55.0% in patients with no statin use. Serious AEs, deaths, and symptomatic confirmed hypoglycemia (fingerstick glucose ≤50mg/dL) were few and similar, irrespective of baseline statin use. CONCLUSIONS: Saxagliptin improves glycemic control and is generally well tolerated in patients with T2DM, irrespective of concomitant statin therapy.

Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus and cardiovascular disease history or cardiovascular risk factors: results of a pooled analysis of phase 3 clinical trials.

OBJECTIVE: This post hoc analysis sought to assess the efficacy, safety, and tolerability of saxagliptin in patients with type 2 diabetes mellitus and cardiovascular (CV) risk factors or disease (CVD). METHODS: Data from 5 randomized controlled trials were pooled to compare saxagliptin 5 mg with placebo: 2 studies of saxagliptin as monotherapy in drug-naïve patients and 1 each of saxagliptin as add-on therapy to metformin, glyburide, or a thiazolidinedione. Analysis was performed according to the following baseline/trial entry criteria: 1) history/no history of CVD; 2) ≥ 2 versus 0 to 1 CV risk factors; 3) statin use versus no statin use; and 4) hypertension versus no hypertension. Change from baseline glycated hemoglobin (HbA1c), fasting plasma glucose, and postprandial glucose levels; and the proportion of patients achieving an HbA1c level < 7% were analyzed (week 24). Safety was assessed by adverse events, hypoglycemia, and body weight. RESULTS: In total, 882 patients received saxagliptin 5 mg and 799 received placebo. Differences in adjusted mean change from baseline HbA1c (95% CI) were greater with saxagliptin compared with placebo in patients with a history of CVD (-0.64% [-0.90 to -0.38]) and no history of CVD (-0.68% [-0.78 to -0.58]); with ≥ 2 CV risk factors (-0.73% [-0.85 to -0.60]) and 0 to 1 CV risk factor (-0.62% [-0.75 to -0.48]); with statin use (-0.70% [-0.89 to -0.52]) and no statin use (-0.66% [-0.77 to -0.56]); and with hypertension (-0.69% [-0.82 to -0.57]) and no hypertension (-0.66% [-0.80 to -0.52]). Saxagliptin was well tolerated, with similar adverse event rates and types compared with placebo. There was a < 1% rate of confirmed hypoglycemia in all groups except in patients with CV history who received placebo (2.1%). CONCLUSION: Saxagliptin improved glycemic measures, resulted in low rates of confirmed hypoglycemia, and was well tolerated in patients with or without CVD and CV risk factors.

Tolerability and efficacy of glycemic control with saxagliptin in older patients (aged ≥ 65 years) with inadequately controlled type 2 diabetes mellitus.

PURPOSE: To assess safety and efficacy of saxagliptin in older patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: This was a post hoc analysis of pooled data from older patients (≥65 years of age) from five 24-week phase III trials: three studies of saxagliptin versus placebo as an add-on therapy to metformin, glyburide, or a thiazolidinedione; and two studies of saxagliptin versus placebo as monotherapy in drug-naïve patients. Separate analyses were conducted on one study of initial combination therapy with saxagliptin plus metformin versus metformin monotherapy in drug-naïve patients. The safety analysis population for the five-study pool included 428 patients ≥ 65 years of age with baseline glycated hemoglobin (HbA(1c)) 7.0% to 10.5% who received saxagliptin 2.5 or 5 mg or placebo, and for the study of initial combination therapy included 69 patients ≥ 65 years of age with baseline HbA(1c) 8.0% to 12.0% who received saxagliptin 5 mg in combination with metformin or metformin monotherapy. The primary efficacy endpoint was change from baseline HbA(1c). RESULTS: In the five-study pool, the differences in the adjusted mean change from baseline HbA(1c) among older patients receiving saxagliptin versus placebo were -0.60% (95% confidence interval [CI], -0.99% to -0.21%) for saxagliptin 2.5 mg and -0.55% (-0.97% to -0.14%) for saxagliptin 5 mg; in the initial combination study, the difference was -1.22% (-2.27% to -0.17%) among older patients receiving saxagliptin 5 mg plus metformin versus metformin monotherapy. The results were generally similar in older and younger patients. Saxagliptin was well tolerated; the incidence and types of adverse events were similar for saxagliptin and comparators. Hypoglycemia was reported in 3.0% to 9.4% of patients receiving saxagliptin (0%-8.0% for comparators) and was confirmed (finger stick glucose ≤ 50 mg/dL, with associated symptoms) in 0% to 0.7% (0%-0.7% for comparators); hypoglycemic episodes did not vary by age category and did not require medical intervention. CONCLUSION: Saxagliptin was effective and well tolerated, with a low risk of hypoglycemia, when used as monotherapy, add-on therapy, or initial combination therapy with metformin in older patients with T2DM.

Efficacy and safety of saxagliptin combination therapy in US patients with type 2 diabetes.

BACKGROUND: The mechanism of action of dipeptidyl peptidase-4 inhibitors, such as saxagliptin, makes them suitable for combination therapy in type 2 diabetes mellitus (T2DM). Genetic, cultural, and environmental differences in individuals from different regions of the world may result in differences in treatment response to oral antidiabetic drugs (OADs). This post-hoc subanalysis assessed the efficacy and safety of saxagliptin as add-on therapy to metformin, glyburide, or a thiazolidinedione in patients with inadequately controlled T2DM in the United States. METHODS: In 3 phase 3 studies of patients with T2DM uncontrolled on monotherapy, 547 adult US patients were randomized to receive saxagliptin (2.5 or 5 mg/d) or placebo as add-on to metformin, glyburide, or a thiazolidinedione (pioglitazone or rosiglitazone). Efficacy was assessed as the change from baseline to week 24 in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial glucose area under the curve (PPG-AUC) and the proportion of patients achieving HbA1c<7.0%. Pooled safety and tolerability data across trials were also analyzed. RESULTS: Reductions from baseline to week 24 in HbA1c were observed in all saxagliptin treatment groups versus placebo: saxagliptin 2.5 or 5 mg plus metformin (mean difference from placebo, -0.87% and -0.89%, respectively), glyburide (-0.51% and -0.52%), or thiazolidinedione (-0.45% and -0.60%). Improvement was also observed in FPG and PPG-AUC. Adverse events for the US cohort were consistent with previously reported data from the 3 trials. The pooled incidence of reported hypoglycemia was 5.3% and 11.4% with saxagliptin 2.5 and 5 mg/d add-on, respectively, versus 6.8% with placebo add-on. CONCLUSIONS: This post-hoc analysis in a cohort of US patients with T2DM uncontrolled on monotherapy suggests that saxagliptin 2.5 or 5 mg as add-on therapy to OADs results in improvement across key glycemic parameters compared with placebo add-on and was generally safe and well tolerated.

Safety and efficacy of saxagliptin added to thiazolidinedione over 76 weeks in patients with type 2 diabetes mellitus.

To assess the long-term efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus inadequately controlled with thiazolidinedione monotherapy, 565 patients were randomised to saxagliptin (2.5 mg or 5 mg) or placebo added to thiazolidinedione over 76 weeks (24-week short-term + 52-week long-term extension period) in this phase 3, double-blind, placebo-controlled trial; 360 patients completed the study. At 76 weeks, adjusted mean changes from baseline HbA(1C) (repeated measures model; 95% CI) for saxagliptin 2.5 mg, 5 mg, and placebo were -0.59% (-0.75, -0.43), -1.09% (-1.26, -0.93), and -0.20% (-0.39, -0.01), respectively (post hoc and nominal p=0.0019 and p<0.0001 for saxagliptin 2.5 mg and 5 mg vs. placebo, respectively). Adverse event frequency was similar between groups. Confirmed hypoglycaemic events were 1.0% and 0% vs. 0.5% for saxagliptin 2.5 mg and 5 mg vs. placebo, respectively. Results should be interpreted with caution given the proportion of patients who discontinued or required glycaemic rescue therapy during the 76-week course of study. Saxagliptin added to thiazolidinedione provided sustained incremental efficacy vs. placebo with little hypoglycaemia for up to 76 weeks and was generally well tolerated.

Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone.

CONTEXT: Due to the natural progression of type 2 diabetes (T2D), most patients require combination therapy to maintain glycemic control. OBJECTIVE: Our objective was to evaluate efficacy and safety of saxagliptin plus thiazolidinedione (TZD) in patients with T2D and inadequate glycemic control on TZD monotherapy. DESIGN: The study was a multicenter, randomized, double-blind, placebo (PBO)-controlled phase 3 trial conducted from March 13, 2006, to October 15, 2007. SETTING: Patients were recruited from 172 outpatient centers. PATIENTS: Patients with inadequately controlled T2D [glycosylated hemoglobin (HbA(1c)) 7.0-10.5%], 18-77 yr, receiving stable TZD monotherapy (pioglitazone 30 or 45 mg or rosiglitazone 4 or 8 mg) for at least 12 wk before screening were eligible. INTERVENTIONS: A total of 565 patients were randomized and treated with saxagliptin (2.5 or 5 mg) or PBO, once daily, plus stable TZD dose for 24 wk. MAIN OUTCOME MEASURES: Primary outcome was change in HbA(1c) from baseline to wk 24. Secondary outcomes were change from baseline to wk 24 in fasting plasma glucose, proportion of patients achieving HbA(1c) less than 7.0%, and postprandial glucose area under the curve. RESULTS: At 24 wk, saxagliptin (2.5 and 5 mg) plus TZD demonstrated statistically significant adjusted mean decreases vs. PBO in HbA(1c) [-0.66% (P = 0.0007) and -0.94% (P < 0.0001) vs. -0.30%] and fasting plasma glucose [-0.8 mmol/liter (P = 0.0053) and -1 mmol/liter (P = 0.0005) vs. -0.2 mmol/liter]. Proportion of patients achieving HbA(1c) less than 7.0% was greater for saxagliptin (2.5 and 5 mg) plus TZD vs. PBO [42.2% (P = 0.001) and 41.8% (P = 0.0013) vs. 25.6%]. Postprandial glucose area under the curve was significantly reduced [-436 mmol x min/liter (saxagliptin 2.5 mg plus TZD) and -514 mmol x min/liter (saxagliptin 5 mg plus TZD) vs. -149 mmol x min/liter (PBO)]. Saxagliptin was generally well tolerated; adverse event occurrence and reported hypoglycemic events were similar across all groups. CONCLUSIONS: Saxagliptin added to TZD provided statistically significant improvements in key parameters of glycemic control vs. TZD monotherapy and was generally well tolerated.

Initiating insulin therapy in type 2 Diabetes: a comparison of biphasic and basal insulin analogs.

OBJECTIVE: Safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 70/30, prebreakfast and presupper) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs (OADs). RESEARCH DESIGN AND METHODS: This 28-week parallel-group study randomized 233 insulin-naive patients with HbA(1c) values >/=8.0% on >1,000 mg/day metformin alone or in combination with other OADs. Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5-6 units BIAsp 70/30 twice daily or 10-12 units glargine at bedtime and titrated to target blood glucose (80-110 mg/dl) by algorithm-directed titration. RESULTS: A total of 209 subjects completed the study. At study end, the mean HbA(1c) value was lower in the BIAsp 70/30 group than in the glargine group (6.91 +/- 1.17 vs. 7.41 +/- 1.24%, P < 0.01). The HbA(1c) reduction was greater in the BIAsp 70/30 group than in the glargine group (-2.79 +/- 0.11 vs. -2.36 +/- 0.11%, respectively; P < 0.01), especially for subjects with baseline HbA(1c) >8.5% (-3.13 +/- 1.63 vs. -2.60 +/- 1.50%, respectively; P < 0.05). More BIAsp 70/30-treated subjects reached target HbA(1c) values than glargine-treated subjects (HbA(1c) 8.5%.

Postprandial versus preprandial dosing of biphasic insulin aspart in elderly type 2 diabetes patients.

Preprandial dosing (within 5 min before meal) and postprandial dosing (15-20 min after meal onset) of NovoLog Mix 70/30 (BIAsp 30, a biphasic formulation of insulin aspart, 30% soluble and 70% protamine-crystallized) were compared in elderly (> or =65 years) type 2 diabetes patients in this open-label, 12-week, crossover study. Ninety-three patients were treated with b.i.d. preprandial injections of BIAsp 30 during a 2-week run-in period and subsequently randomized to a 4-week treatment with either pre- or postprandial b.i.d. BIAsp 30, followed by crossover to the other regimen for 4 weeks. Mean plasma glucose values during a 4-h mealtest at the end of each treatment were similar for pre- and postprandial BIAsp 30 (153 +/- 58 mg/dl and 161 +/- 59 mg/dl, respectively, difference not significant). However, the mean blood glucose increment from self-measured blood glucose values was slightly but significantly greater after postprandial injection than after preprandial injection (treatment difference: 16.3mg/dl; 95% CI: [0.5, 29.3]). Fifty-six percent of patients reported a hypoglycemic episode; postprandial injection did not increase the incidence of hypoglycemia as compared to preprandial injection (113 episodes versus 125 episodes, respectively). For some elderly type 2 diabetes patients, postprandial injection of BIAsp 30 may be an acceptable alternative to standard preprandial injection.

A genome-wide scan for autoimmune thyroiditis in the Old Order Amish: replication of genetic linkage on chromosome 5q11.2-q14.3.

Autoimmune thyroiditis (AITD) is a common disorder characterized by circulating antibodies to epitopes of thyroid tissue and hypothyroidism (Hashimoto's thyroiditis or AITD-hypothyroidism), although many subjects with AITD are euthyroid. Current evidence suggests that AITD is familial and polygenic. We studied AITD in a homogeneous founder Caucasian population, the Old Order Amish of Lancaster County, Pennsylvania. We found autoimmune thyroiditis, defined by the presence of circulating antimicrosomal antibodies, to be relatively common in the Amish, with a prevalence of 22.7%. The prevalence of AITD-hypothyroidism was 9.2%. We performed a genome-wide linkage analysis with 373 short tandem repeat markers in 445 subjects from 29 families. We observed suggestive evidence of linkage of AITD to a locus on chromosome 5q11.2-q14.3 (LOD, 2.30; P = 0.0006 at 94 cM; closest marker, D5S428), a region that was previously reported to be linked to AITD-hypothyroidism in a Japanese study. AITD-hypothyroidism showed a more modest linkage peak to the same region (LOD, 1.46; P = 0.005). Possible linkage (nominal P < 0.01) to autoimmune thyroiditis and/or AITD-hypothyroidism was also detected in five other regions. We conclude that a gene on chromosome 5q11.2-q14.3 is likely to contribute to susceptibility to AITD in the Amish.