Insulin-requiring Type Research Articles

Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk.

A1C is associated with diabetes complications but does not reflect glycemic variability (GV), which may worsen outcomes by inducing inflammation, oxidative stress, and cardiac arrhythmias. We tested whether a glucagon-like peptide 1 agonist-based regimen can reduce GV and cardiometabolic risk markers while maintaining similar A1C levels in people with insulin-requiring type 2 diabetes and high cardiovascular risk. After run-in on metformin and basal-bolus insulin (BBI), 102 participants continued metformin and basal insulin and were randomized to exenatide dosing before the two largest meals (glucacon-like peptide-1 receptor agonist and insulin [GLIPULIN group]) or continuation of rapid-acting insulin analogs (BBI group). Indices of GV by continuous glucose monitoring (CGM), hypoglycemia, weight, risk markers, and cardiac arrhythmias were assessed. The primary end point was change in glucose coefficients of variation (CV) by CGM from baseline to 26 weeks. At randomization, the median A1C was 7.3% (57 mmol/mol) for GLIPULIN and 7.4% (56.3 mmol/mol) for BBI, and glucose CVs were 30.3 for BBI and 31.9 for GLIPULIN. At 26 weeks, A1C levels were similar (7.1% [54 mmol/mol] vs. 7.2% [55 mmol/mol]), whereas mean CV improved with GLIPULIN (-2.4 vs. 0.4, P = 0.047). Other GV indices followed similar nonsignificant patterns of improvement with GLIPULIN. There were no differences in hypoglycemic events during CGM or arrhythmias during electrocardiographic monitoring. On-trial changes in body weight (-4.8 kg vs. +0.7 kg, P < 0.001), alanine aminotransferase (P = 0.0002), and serum amyloid A (P = 0.023) favored GLIPULIN. GLIPULIN reduced GV, weight, and some cardiometabolic risk markers while maintaining equivalent A1C levels versus BBI and might improve clinical outcomes in a larger trial.

Diabetes and the brain: More information needed

Hyperglycemia is clearly associated with the longterm risk of diabetes-related microvascular and macrovascular complications. Treatment to reduce hyperglycemia, as determined by hemoglobin A1c (HbA1c), reduces the occurrence and slows the progression of retinopathy, nephropathy, and neuropathy in adults [1] and adolescents [2,3] as well as the macrovascular complications [4]. Despite overall improved glycemic control from newer diabetes management technologies that have developed during the last three decades (insulin analogs, self-blood glucose monitoring, insulin pumps, and continuous glucose monitoring [CGM] sensors), hypoglycemia continues to be a limiting factor in achieving a euglycemic state in insulin-treated (type 1 and insulin-requiring type 2) diabetes mellitus [5]. Even today, with the best of technologies available, persons with type 1 diabetes mellitus (T1DM) spend a significant portion of each day hyperglycemic and/or hypoglycemic. This is clear from many studies, most notably from the JDRF CGM Study [6] in which an average of 395 min (6.5 hr) of the day were spent with blood glucoses (BG) >180 mg/dL, 101 min (1.7 hr) with BG >250 mg/dL and 60 min (1 hr) of the day with BGs 180 mg/dL, 268 min (4.5 hr) with BG >250 mg/dL and 47 min (0.8 hr) with BG <70 mg/dL. Nearly half the day, on average, was spent either hypoor hyperglycemic. In years past, when hypoglycemia was considered to be the major contributor to cognitive deficits in children with diabetes, we were satisfied with allowing a higher glycemic target in children so as to avoid hypoglycemia. Coupling the observations from the JDRF CGM study with the associated cognitive impairment in either hypoglycemic or hyperglycemic state leaves caregivers of patients with T1DM with an important challenge: What is the best range to target blood glucose to maximize the benefits of glycemic control for the prevention of the long-term vascular complications while minimizing the potential for cognitive and CNS complications associated with both hypoglycemia and hyperglycemia? In this issue of the Journal of Pediatric Neuroradiology, Kaufmann et al. report their findings from a crosssectional study using cognitive testing and brain MRI in 30 “pediatric patients” (6 20 years old) with T1DM and 19 similarly-aged non-diabetic controls. The T1DM subjects were analyzed in two groups, one (n = 15) with HbA1c < 8.0% (“low HbA1c group”) and the other with *Address for correspondence: Neil H. White, Division of Endocrinology & Diabetes, Co-Unit Leader, Patient-Oriented Research Unit (PORU), Director, Pediatric Clinical Research Unit (PCRU), Department of Pediatrics, 660 South Euclid Avenue, Box 8116, St. Louis, MO 63110, USA. Tel.: +1 314 286 1157; Fax: +1 314 286 1187; E-mail: white_n@kids.wustl.edu. Journal of Pediatric Neuroradiology 1 (2012) 3–5 DOI 10.3233/PNR-2012-002 IOS Press 3

Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes.

Glycemic variability may contribute to adverse medical outcomes of type 2 diabetes, but prior therapies have had limited success in controlling glycemic fluctuations, and the hypothesis has not been adequately tested. People with insulin-requiring type 2 diabetes and high cardiovascular risk were enrolled during a run-in period on basal-bolus insulin (BBI), and 102 were randomized to continued BBI or to basal insulin with a prandial GLP-1 receptor agonist (GLIPULIN) group, each seeking to maintain HbA(1c) levels between 6.7% and 7.3% (50-56 mmol/mol) for 6 months. The primary outcome measure was glycemic variability assessed by continuous glucose monitoring; other measures were HbA(1c), weight, circulating markers of inflammation and cardiovascular risk, albuminuria, and electrocardiographic patterns assessed by Holter monitoring. At randomization, the mean age of the population was 62 years, median duration of diabetes 15 years, mean BMI 34 kg/m(2), and mean HbA(1c) 7.9% (63 mmol/mol). Thirty-three percent had a prior cardiovascular event, 18% had microalbuminuria, and 3% had macroalbuminuria. At baseline, the continuous glucose monitoring coefficient of variation for glucose levels was similar in both groups. FLAT-SUGAR is a proof-of-concept study testing whether, in a population of individuals with type 2 diabetes and high cardiovascular risk, the GLIPULIN regimen can limit glycemic variability more effectively than BBI, reduce levels of cardiovascular risk markers, and favorably alter albuminuria and electrocardiographic patterns. We successfully randomized a population that has sufficient power to answer the primary question, address several secondary ones, and complete the protocol as designed.

Bariatric surgery and diabetes: Implications of type 1 versus insulin-requiring type 2.

To report the impact of bariatric surgery on metabolic outcomes in patients with type 1 diabetes (DM1) versus insulin-requiring type 2 diabetes mellitus (IRDM2). Ten subjects with DM1 were compared with 118 subjects with IRDM2 at baseline and at 1 and 2 years post-bariatric surgery for: anthropometric measures, HbA1c, and number of medications (anti-hyperglycemic, anti-hypertensive, lipid-lowering). DM1 and IRDM2 groups lost similar amounts of weight 2 years post-bariatric surgery (39.5 ± 14.7 kg vs. 40.3 ± 24.4 kg). IRDM2 subjects had significant improvements in HbA1c (7.8% ± 1.4% vs. 6.8% ± 1.4%, P value <0.0001) and decreases in number of anti-hyperglycemic (2.4 ± 0.8 vs. 0.7 ± 0.8, P value <0.0001), anti-hypertensive (2.2 ± 1.3 vs. 1.3 ± 1.2, P value <0.0001), and lipid-lowering (1.1 ± 0.8 vs. 0.6 ± 0.6, P value <0.0001) medications. DM1 subjects had no improvement in HbA1c (8.2% ± 1.6% vs. 7.8% ± 0.9%) or use of anti-hypertensive medications (2.1 ± 1.4 vs. 2.3 ± 1.5). Their use of lipid-lowering medications improved (1.0 ± 0.5 vs. 0.5 ± 0.8, P value 0.04). Our study suggests that improved glycemic control may not be an expected outcome when considering bariatric surgery in patients with DM1; however, additional investigation is warranted.

First fixed-ratio combination of insulin degludec and liraglutide for the treatment of type 2 diabetes.

When oral hypoglycemic agents do not successfully suppress hyperglycemia, the traditional approach has been to add insulin injections. With the coming of glucagon-like peptide 1 (GLP-1) receptor agonists carrying the benefits of weight loss and reduced risk of hypoglycemia, it has been suggested that GLP-1 agents should be used instead. There is equivalent lowering of HbA1c with either treatment. Insulin therapy is associated with hypoglycemia and weight gain while GLP-1 receptor agonists promote weight loss. Gastrointestinal (GI) intolerance is the chief obstacle to GLP-1 treatment. The combined use of basal insulin and GLP-1 receptor agonists results in improved glycemic control and mitigates weight gain. The recent approval of insulin degludec/liraglutide administered in a fixed ratio combination is unique not simply for the additive benefits of the two agents, but because it now permits adjustable dosing of liraglutide together with insulin, providing better glucose control than with either agent alone at lower dose levels. Lower dosage of insulin degludec reduces the risk of hypoglycemia. Liraglutide combats the weight gain that accompanies the introduction of insulin therapy, and a reduced dose of liraglutide induces less GI intolerance. This first combined basal insulin-GLP-1 receptor agonist combination represents a conceptual advance in the treatment of insulin-requiring type 2 diabetes.

Glycosylated hemoglobin level and number of oral antidiabetic drugs predict whether or not glycemic target is achieved in insulin-requiring type 2 diabetes

AimsFactors predicting success (glycosylated hemoglobin (A1C)<7%) with insulin therapy in patients with insulin-requiring type 2 diabetes need to be identified. MethodsA retrospective, multi-center, observational study was conducted for outpatients with oral antidiabetic drug (OAD)-treated type 2 diabetes whose A1C levels remained above 7%. Patients were begun on basal insulin between January 2005 and December 2006. Biochemical variables and demographic data were collected before and after 52 weeks of insulin therapy. ResultsA total of 565 patients (age, 60.4±11.9 years; A1C levels, 10.11 ±1.81%; duration of diabetes, 11.5±6.8 years) were studied. By study end, 63 patients (11.2%) had achieved the glycemic goal (A1C<7%). The glycemic goal attainment rate was only 9.1% in patients with A1C>8.8% and who were taking >2 OADs at baseline. The highest rate (32.7%) of successful glycemic control was observed in the group of patients with A1C ≤ 8.8% and who used ≤ 2 OADs at baseline. ConclusionsInsulin-naïve diabetic patients with A1C>8.8%, especially those who are taking >2 OADs, have small chance to achieve good glycemic control with adding only basal insulin therapy.

A Comparison of Internet Monitoring with Continuous Glucose Monitoring in Insulin-Requiring Type 2 Diabetes Mellitus

To compare the effects of real-time continuous glucose monitoring (RT-CGM) and an Internet blood glucose monitoring system (IBGMS) on glycated hemoglobin levels in patients with type 2 diabetes mellitus treated with insulin. Fifty-seven patients with type 2 diabetes treated with insulin were assigned randomly to 1 of 2 groups. Group 1 had the results of their self-monitoring of blood glucose level monitored biweekly using an IBGMS. Group 2 used RT-CGM and were monitored biweekly. Both groups used a secure website to upload data and to receive feedback from their endocrinologist. A1C and laboratory test results were collected at 0, 3 and 6 months. The baseline parameters were not significantly different. After a 6-month follow-up period, both IBGMS and RT-CGM showed significant within-group improvements in A1C level. In the IBGMS group, the A1C level decreased from 8.79%±1.25% to 7.96%±1.30% (p<0.05). The RT-CGM group decreased from 8.80%±1.37% to 7.49%±0.70% (p<0.001). IBGMS and RT-CGM did not show significantly different A1C levels at baseline, 3 and 6 months (p>0.05). The use of both IBGMS and RT-CGM significantly improved A1C levels in patients with type 2 diabetes treated with insulin in a randomized trial over a 6-month period. There were no significant differences in A1C values between groups after 6 months.

Pancreas and Islet Transplantation

Pancreas and Islet Transplantation

Associations ofβ-Cell Function and Insulin Resistance with Youth-Onset Type 2 Diabetes and Prediabetes Among Asian Indians

This study examined β-cell function and insulin resistance (homeostasis model assessment-insulin resistance [HOMA-IR]) in Asian Indian youth with type 2 diabetes mellitus (T2DM-Y) and prediabetes. Eighty-two subjects with non-insulin-requiring type 2 diabetes and age of onset below 25 years were recruited within 18 months of diagnosis and compared with age- and sex-matched subjects with prediabetes (n=31) and normal glucose tolerance (NGT) (n = 83). Body mass index (BMI) and waist circumference were measured, and blood samples were taken in the fasting state and after 30, 60, 90, and 120 min of an oral glucose load for assessment of plasma glucose and insulin levels. Insulin sensitivity/resistance measures was calculated by using the reciprocal of the fasting insulin, the HOMA-IR equation, and the composite whole body insulin sensitivity index (Matsuda Index), and β-cell function was calculated by the oral disposition index (DIo). T2DM-Y and prediabetes subjects had higher BMI, waist circumference, and fasting insulin than NGT subjects (P<0.05 for each). The 30-min insulin levels were lower in T2DM-Y and higher in prediabetes subjects compared with NGT (57 and 140 vs. 129 μIU/mL, P<0.001). The T2DM-Y group had greater insulin resistance (HOMA-IR, 1.87 vs. 0.97; P<0.05) and lower β-cell function (DIo, 0.36 vs. 3.28; P<0.001) than NGT. In separate models, the Matsuda Index and DIo were independently associated with prediabetes and T2DM-Y (P<0.05). However, when both were included together, only DIo remained associated with T2DM-Y, whereas both DIo and Matsuda Index were associated with prediabetes (P<0.05). When controlled for adiposity (BMI and waist circumference), an association was observed but in opposite directions, with waist being positively associated with prediabetes (P = 0.016) and BMI negatively associated with T2DM-Y (P = 0.009). Among Asian Indians, β-cell dysfunction appears to be more strongly associated with T2DM-Y than insulin resistance.

Pramlintide: profile of an amylin analog

Amylin is a naturally occurring hormone that regulates food intake and postprandial glucose excursions. Amylin is synthesized in the β cell and cosecreted with insulin. Type 1 diabetes and insulin-requiring Type 2 diabetes are amylin-deficient as well as insulin-deficient states. Pramlintide is a synthetic amylin analog that is used for replacement therapy. Pramlintide therapy slows diabetes-mediated accelerated gastric emptying and restores meal-mediated suppression of glucagon secretion in patients with diabetes. Amylin receptors are primarily located in the CNS, which mediates all of its effects including decreases in food intake. In patients with diabetes, pramlintide treatment reduces hemoglobin A1C (HbA1c) 0.3–0.7% and decreases bodyweight. Side effects include nausea and hypoglycemia. Both can be minimized by an appropriate titration program. Recent pramlintide studies address improvements in delivery systems, use in pediatric and Type 2 diabetic populations, patient treatment satisfaction and new insights into its mechanisms of action.

An evaluation of insulin therapy initiation among patients with type 2 diabetes attending a public health facility in South Africa

AbstractBackground: Clinically effective interventions that could reduce diabetic patients' risk of long-term complications are needed to contain the rising cost of diabetes care associated with the increasing prevalence of this condition. Good glycaemic control needs to be rapidly attained and maintained by the appropriate initiation and adjustment of glucose-lowering therapy. In patients with insulin-requiring type 2 diabetes who are not at goal glycaemia, this translates to the initiation and intensification of insulin therapy. The aim of this study was to evaluate the appropriateness of the initiation of insulin therapy in patients with poorly controlled insulin-requiring type 2 diabetes.Method: This descriptive retrospective study evaluated treatment regimens, dose adjustments and glycated haemoglobin A1c (HbA1c) measurements extracted from records of patients with type 2 diabetes suitable for inclusion. The observation period spanned the 24 months retrospective to study start. Data collected were tr...

New developments to optimize postprandial glucose control with insulin in patients with diabetes

SUMMARY Many patients with Type 1 or insulin-requiring Type 2 diabetes fail to achieve the widely recommended glycemic target of HbA1c below 7%. Insufficient control of postprandial glucose excursion plays an important role in this failure. The pharmacological profile of rapid-acting insulin analogs is still far from mimicking the physiological profile of endogenous insulin secretion. Several products are under development that aim to bring this goal closer. These developments include the use of jet injectors for insulin administration, coadministration of hyaluronidase, insulin agents that are resistant to hexamer formation, and insulin products that use an alternative route of administration. This review provides an overview of recent developments and discusses potential benefits with respect to postprandial glucose control.

Erlotinib appears to produce prolonged remission of insulin-requiring type 2 diabetes associated with metabolic syndrome and chronic kidney disease

Patients with metabolic syndrome are at higher risk for type 2 diabetes and for chronic kidney disease. Metformin is the oral medication of choice for the treatment of type 2 diabetes in the absence of chronic kidney disease. There is a need for another oral glucose lowering agent for use in metabolic syndrome with type 2 diabetes and chronic kidney disease. We submit the first report of erlotinib, a once-daily oral medication for the treatment of non-small-cell lung cancer associated with specific genetic mutations, appearing to eliminate the need for insulin in insulin-requiring type 2 diabetes associated with metabolic syndrome and chronic kidney disease. The mechanism by which erlotinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor may improve glycaemic control is unknown. Potential possibilities are explored.

Phase I (Safety) Study of Autologous Tolerogenic Dendritic Cells in Type 1 Diabetic Patients

OBJECTIVEThe safety of dendritic cells to selectively suppress autoimmunity, especially in type 1 diabetes, has never been ascertained. We investigated the safety of autologous dendritic cells, stabilized into an immunosuppressive state, in established adult type 1 diabetic patients.RESEARCH DESIGN AND METHODSA randomized, double-blind, phase I study was conducted. A total of 10, otherwise generally healthy, insulin-requiring type 1 diabetic patients between 18 and 60 years of age, without any other known or suspected health conditions, received autologous dendritic cells, unmanipulated or engineered ex vivo toward an immunosuppressive state. Ten million cells were administered intradermally in the abdomen once every 2 weeks for a total of four administrations. The primary end point determined the proportion of patients with adverse events on the basis of the physician’s global assessment, hematology, biochemistry, and immune monitoring for a period of 12 months.RESULTSThe dendritic cells were safely tolerated. There were no discernible adverse events in any patient throughout the study. Other than a significant increase in the frequency of peripheral B220+ CD11c− B cells, mainly seen in the recipients of engineered dendritic cells during the dendritic cell administration period, there were no statistically relevant differences in other immune populations or biochemical, hematological, and immune biomarkers compared with baseline.CONCLUSIONSTreatment with autologous dendritic cells, in a native state or directed ex vivo toward a tolerogenic immunosuppressive state, is safe and well tolerated. Dendritic cells upregulated the frequency of a potentially beneficial B220+ CD11c− B-cell population, at least in type 1 diabetes autoimmunity.

Experimental testing of skin reactions to insulin detemir in diabetes patients naïve to insulin detemir

Sporadic reports on immediate and delayed cutaneous reactions to insulin detemir, a modern insulin analogue, have raised unsupported claims of allergy of type I, III and IV. The purpose of this experimental study using a provocative design was to elucidate the potential mechanisms behind such skin reactions. A total of 40 patients with type 1 diabetes or insulin-requiring type 2 diabetes, all naïve to insulin detemir, were injected on the thigh with 0.l mL of insulin detemir (Levemir(®)) administered with an 8 mm needle at three different depths, i.e. intradermal, subdermal and subcutaneously. Saline was injected as control. Any cutaneous reactions were assessed after 10 and 30 min, after 24 and 48 h and after 7 days. Histopathology of positive reactions on day 7 was obtained. The study was randomized, controlled, double-blinded, and conducted in accordance with ICH-GCP guidelines. Blood flow was recorded with the Periflux PF5010, and skin colour (a*) with the DSMII colorimeter. Clinical reading, flowmetry and colorimetry consistently showed delayed reactions after intradermal insulin injection (35 of 40 patients reacted with mainly weak reactions, P<0.05), peaking after 48 h, contrasting no special reaction immediately after injection, except for reactions attributed to needle trauma. A total of 22 patients reacted on subdermal injection and 21 on subcutaneous injection. Histopathology on day 7 from 22 reactions in 15 patients showed a consistent pattern of inflammation with eosinophilia as typically observed in adverse skin reactions to a variety of medicines. Reactions were interpreted as non-specific biologic responses to the insulin different from direct toxic actions and classical allergic reaction patterns. Only one person registered itch/discomfort. A prick test vs. histamine reference excluded insulin detemir to be a pharmacological histamine releaser. Thus, provocative testing with insulin detemir produced delayed skin reaction but no immediate reaction. Measurement of circulating insulin detemir-specific antibodies by RIA before and after 3 months showed no increase. Non-allergic delayed skin reactions from intradermal and, to a minor degree, subdermal and subcutaneous injections of insulin detemir were frequent in this experimental study and showed a consistent histology pattern of inflammation with eosinophilia. Immediate reactions were not produced. The reactions are unlikely to be specific for insulin detemir, and other insulins should be studied in a similar provocative design.

Lean Mass Predicts Hip Geometry in Men and Women With Non–Insulin-Requiring Type 2 Diabetes Mellitus

Persons with type 2 diabetes mellitus (T2DM) are at increased risk for hip fracture despite normal bone mineral density (BMD). The contribution of body composition to hip geometry, a measure of hip strength, has not been studied in T2DM. We hypothesized that lean mass would predict hip geometry. Subjects (n = 134) for this cross-sectional analysis were men and women aged 56 ± 6 yr with non–insulin-requiring T2DM. Fat and lean mass were measured with dual-energy X-ray absorptiometry (DXA). Abdominal fat was measured with magnetic resonance imaging. Hip geometry parameters including section modulus, cross-sectional area, and buckling ratio were estimated from DXA using validated formulae. Subjects had normal BMD, elevated body mass indices (29–41 kg/m 2), and controlled T2DM (hemoglobin A1c: 5.1–8.3%). In bivariate analysis, lean mass was positively associated with section modulus and cross-sectional area in both sexes ( r = 0.36–0.55, p < 0.05). In multivariate analyses, lean mass remained a significant predictor of all hip strength estimates in both sexes. In women alone, fat mass predicted parameters of hip strength. These data demonstrate that lean mass is significantly associated with hip strength in subjects with non–insulin-requiring T2DM. Resistance exercises that build lean mass may be an intervention for hip fracture prevention in T2DM, although additional research is needed.

Home Blood Glucose Monitoring in Type 2 Diabetes

The Diabetes Control and Complications Trial (DCCT) (1) would not have been possible without the advent of several technologies, including self-monitoring of blood glucose (SMBG). After the results of that landmark study were reported in 1993, SMBG was considered the standard of care for type 1 diabetic patients. The same was true for insulin-requiring type 2 diabetic patients after the report of the UK Prospective Diabetes Study (UKPDS) in 1998 (2). However, cost pressures have now caused some to question SMBG in type 1 diabetes (3), and we continue to struggle with conflicting evidence for those patients with type 2 diabetes not receiving insulin. The fundamental problem has been difficulty in trial design with many of the challenges carrying over from clinical trials to clinical practice. For example, is the patient with type 2 diabetes even willing and able to perform SMBG? And, based on the glucose data, is the patient engaged enough to make behavioral changes that would improve glucose control? And even for those individuals who are able to make significant lifestyle changes, will they be willing to initiate insulin therapy if indicated? From the provider's perspective, is there time to review the data and potentially intensify therapy with that information? Can the provider even easily access the data, especially if there is a large amount of information in the 2 or 3 weeks before a clinic appointment? If the clinician cannot download the data, will the patient be willing to share the information either with a paper logbook or perhaps a computerized tool such as a spreadsheet or even a smart-phone app? What becomes clear is that for data to …

A Prospective Trial of U500 Insulin Delivered by Omnipod in Patients With Type 2 Diabetes Mellitus and Severe Insulin Resistance

To test the effectiveness and safety of U500 regular insulin delivered by continuous subcutaneous insulin infusion (CSII) via the Omnipod insulin delivery system in patients with uncontrolled type 2 diabetes mellitus and severe insulin resistance. In this prospective, 1-year, proof-of-concept trial, patients with insulin-requiring type 2 diabetes who had a hemoglobin A1c level of 7.0% or higher and severe insulin resistance (average insulin requirement, 1.74 units of insulin per kilogram each day; range, 1.4 to 2.64 units of insulin per kilogram [average insulin dose, 196.4 units daily]) were identified at routine office visits at Mountain Diabetes and Endocrine Center in Asheville, North Carolina, between December 2007 and August 2008. All patients had been on intensive insulin therapy with or without oral agents for more than 3 months. All patients were switched from baseline failed therapy to U500 regular insulin by continuous subcutaneous insulin infusion via Omnipod. Effectiveness was assessed by hemoglobin A1c measurement and 72-hour continuous glucose monitoring at baseline and at weeks 13, 26, and, 52 and by treatment satisfaction assessed by the Insulin Delivery Rating System Questionnaire at baseline and at week 52 while on U500 via Omnipod. Twenty-one adults were enrolled (mean age, 54 years; mean duration of diabetes, 4 years; mean body mass index, 39.4 kg/m2; mean insulin requirement, 1.7 U/kg per day; and mean hemoglobin A1c, 8.6%) whose previous treatment with U100 insulin regimens had failed. Twenty patients completed the study. Treatment with U500 insulin via Omnipod significantly reduced hemoglobin A1c by 1.23% (P<.001) and significantly increased the percentage of time spent in the blood glucose target range (70-180 mg/dL) by 70.75% as assessed by continuous glucose monitoring (P<.001) without a significant increase in hypoglycemia. Patients were satisfied with treatment with U500 insulin via Omnipod, and 14 patients elected to remain on treatment at study completion. U500 insulin delivered subcutaneously continuously via Omnipod is a safe and effective method of insulin delivery in the very insulin-resistant type 2 diabetic population.

New Features and Performance of a Next-Generation SEVEN-Day Continuous Glucose Monitoring System with Short Lag Time

The purpose of this study was to evaluate new features and performance of the SEVEN PLUS System (DexCom, Inc., San Diego, CA), a real-time continuous glucose monitoring (CGM) device. This study is the first to evaluate the SEVEN PLUS device. Fifty-three subjects were enrolled at three U.S. centers; 43 (81%) of the subjects had type 1 diabetes mellitus, and 10 (19%) had insulin-requiring type 2 diabetes mellitus. Subjects inserted and wore either one or two sensors for 7 days. A subgroup (n = 18) wore two sensors to track precision. Subjects participated in one 8-h in-clinic session with blood draws every 15 min on study Day 1, 4, or 7 to collect laboratory reference YSI instrument (YSI, Yellow Springs, OH) and self-measured plasma glucose (SMPG) reference measurements. For the remainder of the week, CGM was used as an adjunct to SMPG during home use. The overall median absolute relative difference (ARD) versus YSI was 13.0%. Zones A and B of the Clarke Error Grid of CGM measurements were 73.8% and 22.1%, respectively. Precision ARD was 15.3 +/- 6.2% (mean +/- SD). The median ARD versus SMPG was 12.1%. Sensor life (89% lasted 7 days) was improved compared to the SEVEN device. The lag time obtained with various statistical measures between CGM and YSI were similar and estimated as a median of 8 min (interquartile range, 11 min) using the Pearson correlation coefficient. No serious adverse events or infectious complications were reported. The performance of this new system compares favorably to the previous SEVEN device in terms of accuracy, precision, lag time, sensor life, and rate of data capture.

The role of modifiable pre‐pregnancy risk factors in preventing adverse fetal outcomes among women with type 1 and type 2 diabetes

We investigated the fetal outcomes of pregnancy in women with pre-existing diabetes in relation to pre-pregnancy risk factors using a community-based cohort of women in Tayside, Scotland. There were 211 pregnancies in 132 women with insulin-requiring type 1 and 2 diabetes between January 1993 and December 2005. Adverse fetal outcome was classified as spontaneous miscarriage, termination for medical reasons, stillbirth, neonatal death, or congenital malformation and occurred in 61 (29%) pregnancies. Mothers with poor glycemic control pre-conceptually and at booking (HbA(1c)=7.5%) had almost a three-fold increase in adverse fetal outcome compared with mothers having fair control, odds ratio (OR) 2.59 (95% CI 1.11-6.03), and 2.71 (95% CI 1.39-5.28), respectively. Mothers who were still smoking at the booking visit had a two-fold increase in adverse fetal outcome (OR 2.12, 95% CI 1.09-4.10). Further improvement in the management of diabetes and pregnancy is needed through enhanced preconception services addressing the full spectrum of modifiable risk factors.