OBJECTIVE -Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucoseand lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone.RESEARCH DESIGN AND METHODS -We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n ϭ 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n ϭ 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals.RESULTS -Triglyceride levels were reduced by 51.9 Ϯ 7.8 mg/dl with pioglitazone, but were increased by 13.1 Ϯ 7.8 mg/dl with rosiglitazone (P Ͻ 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 Ϯ 0.5 vs. 2.4 Ϯ 0.5 mg/dl; P Ͻ 0.001) and the increase in LDL cholesterol was less (12.3 Ϯ 1.6 vs. 21.3 Ϯ 1.6 mg/dl; P Ͻ 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P Ͻ 0.001). LDL particle size increased more with pioglitazone (P ϭ 0.005).CONCLUSIONS -Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size. Diabetes Care 28:1547-1554, 2005T wo core metabolic defects contribute to the development of type 2 diabetes: relative insulin insufficiency and insulin resistance. Approximately 92% of patients with type 2 diabetes demonstrate insulin resistance (1). Even in the absence of overt hyperglycemia, insulin resistance is associated with a cluster of abnormalities that increase the risk for cardiovascular disease (CVD), including dyslipidemia, increased expression of inflammatory markers, activation of procoagulants, hemodynamic changes, and endothelial dysfunction (2,3).The dyslipidemia associated with insulin resistance and type 2 diabetes is characterized by elevated triglycerides and decreased HDL cholesterol (4 -6). Although LDL cholesterol may not be elevated in type 2 diabetes, an increase in the proportion of small, dense, and potentially more atherogenic LDL cholesterol particles is observed (7). In addition to LDL cholesterol, elevated triglyceride levels and reduced HDL cholesterol levels are both risk factors for coronary heart disease (CHD) (8 -11). Compared with nondiabetic individuals, patients with type 2 diabetes have a two-to fourfold high...

Type 2 Diabetes Mellitus (HEART2D) is a multinational, randomized, controlled trial designed to compare the effects of prandial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction (AMI).RESEARCH DESIGN AND METHODS -Patients (type 2 diabetes, aged 30 -75 years) were randomly assigned within 21 days after AMI to the 1) prandial strategy (PRANDIAL) (three premeal doses of insulin lispro targeting 2-h postprandial blood glucose Ͻ7.5 mmol/l) or the 2) basal strategy (BASAL) (NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose Ͻ6.7 mmol/l).RESULTS -A total of 1,115 patients were randomly assigned (PRANDIAL n ϭ 557; BASAL n ϭ 558), and the mean patient participation after randomization was 963 days (range 1-1,687 days). The trial was stopped for lack of efficacy. Risks of first combined adjudicated primary cardiovascular events in the PRANDIAL (n ϭ 174, 31.2%) and BASAL (n ϭ 181, 32.4%) groups were similar (hazard ratio 0.98 [95% CI 0.8 -1.21]). Mean A1C did not differ between the PRANDIAL and BASAL groups (7.7 Ϯ 0.1 vs. 7.8 Ϯ 0.1%; P ϭ 0.4) during the study. The PRANDIAL group showed a lower daily mean postprandial blood glucose (7.8 vs. 8.6 mmol/l; P Ͻ 0.01) and 2-h postprandial blood glucose excursion (0.1 vs. 1.3 mmol/l; P Ͻ 0.001) versus the BASAL group. The BASAL group showed lower mean fasting blood glucose (7.0 vs. 8.1 mmol/l; P Ͻ 0.001) and similar daily fasting/premeal blood glucose (7.7 vs. 7.3 mmol/l; P ϭ 0.233) versus the PRANDIAL group.CONCLUSIONS -Treating diabetic survivors of AMI with prandial versus basal strategies achieved differences in fasting blood glucose, less-than-expected differences in postprandial blood glucose, similar levels of A1C, and no difference in risk for future cardiovascular event rates.

OBJECTIVETo compare effects of LY2605541 versus insulin glargine on daily mean blood glucose as part of a basal-bolus regimen for type 1 diabetes.RESEARCH DESIGN AND METHODSIn this randomized, Phase 2, open-label, 2 × 2 crossover study, 137 patients received once-daily basal insulin (LY2605541 or glargine) plus mealtime insulin for 8 weeks, followed by crossover treatment for 8 weeks. Daily mean blood glucose was obtained from 8-point self-monitored blood glucose profiles. The noninferiority margin was 10.8 mg/dL.RESULTSLY2605541 met noninferiority and superiority criteria compared with insulin glargine in daily mean blood glucose (144.2 vs. 151.7 mg/dL, least squares mean difference = −9.9 mg/dL [90% CI −14.6 to −5.2], P < 0.001). Fasting blood glucose variability and A1C were reduced with LY2605541 compared with insulin glargine (both P < 0.001). Mealtime insulin dose decreased with LY2605541 and increased with insulin glargine. Mean weight decreased 1.2 kg with LY2605541 and increased 0.7 kg with insulin glargine (P < 0.001). The total hypoglycemia rate was higher for LY2605541 (P = 0.04) and the nocturnal hypoglycemia rate was lower (P = 0.01), compared with insulin glargine. Adverse events (including severe hypoglycemia) were similar, although more gastrointestinal-related events occurred with LY2605541 (15% vs. 4%, P < 0.001). Mean changes (all within normal range) were higher for alanine aminotransferase, aspartate aminotransferase, triglycerides, and LDL-cholesterol and lower for HDL-cholesterol with LY2605541 compared with insulin glargine (all P < 0.02).CONCLUSIONSIn type 1 diabetes, compared with insulin glargine, LY2605541, a novel, long-acting basal insulin, demonstrated greater improvements in glycemic control, increased total hypoglycemia, and reduced nocturnal hypoglycemia, as well as reduced weight and lowered mealtime insulin doses.

BackgroundDiabetes mellitus increases the rate of vaginal colonization and infection with Candida speciesMethodsWe surveyed women with diabetes receiving care at either an urban or suburban diabetes clinic to examine the relationship between vaginal Candida colonization, diabetes type and duration, and HbA1c level. 101 participants completed the self-administered questionnaire and self-collected a vaginal swab for Candida culture. Candida colonization was similar by age and race.ResultsType 1 diabetics were three times as likely as type 2 diabetics to be colonized with any Candida species (OR = 3.4; 95% CI: 1.03, 11.41; p = 0.04); even after adjusting for abnormal HbA1c, which had an independent effect (OR = 1.4; 95% CI: 1.04, 1.76; p = 0.02). Recent antibiotic use (OR = 4.5; 95% CI: 1.18, 16.79; p = 0.03), lifetime history of chlamydia (OR = 5.8; 95% CI: 1.09, 30.54; p = 0.04), and performing oral sex during the past 2 weeks (OR = 4.9; 95% CI:0.84, 28.27; p = 0.08) were also associated with Candida carriage after adjusting for diabetic type and abnormal HbA1c. C. albicans was isolated from the majority of colonized type 1 participants (56%), while C. glabrata was the most common isolate among colonized type 2 participants (54%).ConclusionsImproving glucose control and possibly modifying sexual behavior may reduce risk of Candida colonization, and potentially symptomatic infection, among women with diabetes.

OBJECTIVETo evaluate whether LY2605541 results in lower fasting blood glucose (FBG) versus insulin glargine (GL).RESEARCH DESIGN AND METHODSThis 12-week, randomized, open-label, Phase 2 study enrolled patients with type 2 diabetes (hemoglobin A1c [A1C] ≤ 10.5%), taking metformin and/or sulfonylurea with GL or NPH insulin once daily. Patients converted to morning insulin administration during lead-in were randomized 2:1 from GL (n = 248) or NPH insulin (n = 39) to LY2605541 (n = 195) or GL (n = 95) once daily in the morning.RESULTSAt 12 weeks, FBG (mean ± SE) was similar with LY2605541 and GL (118.2 ± 2.0 mg/dL [6.6 ± 0.1 mmol/L] vs. 116.9 ± 2.7 mg/dL [6.5 ± 0.2 mmol/L], P = 0.433) as was A1C (7.0 ± 0.1 vs. 7.2 ± 0.1%, P = 0.279). Intraday blood glucose variability was reduced with LY2605541 (34.4 vs. 39.1 mg/dL [1.9 vs. 2.2 mmol/L], P = 0.031). LY2605541 patients had weight loss (−0.6 ± 0.2 kg, P = 0.007), whereas GL patients gained weight (0.3 ± 0.2 kg, P = 0.662; treatment difference: −0.8 kg, P = 0.001). The incidence and rate of both total hypoglycemia and nocturnal hypoglycemia were comparable between LY2605541 and GL, although, LY2605541 had a 48% reduction in nocturnal hypoglycemia after adjusting for baseline hypoglycemia (P = 0.021). Adverse events were similar across treatments. Alanine aminotransferase and aspartate aminotransferase remained within normal range but were significantly higher with LY2605541 (P ≤ 0.001).CONCLUSIONSIn patients with type 2 diabetes, LY2605541 and GL had comparable glucose control and total hypoglycemia rates, but LY2605541 showed reduced intraday variability, lower nocturnal hypoglycemia, and weight loss relative to GL.

OBJECTIVE -There are national mandates to reduce blood pressure (BP) to Ͻ130/85 mmHg, LDL cholesterol to Ͻ100 mg/dl, and HbA 1c to Ͻ7% and to institute aspirin therapy in patients with diabetes. The objective of this study was to determine the proportion of patients in urban institutions with diabetes and hypertension who meet these treatment goals.RESEARCH DESIGN AND METHODS -Using American Diabetes Association (ADA) guidelines, we evaluated the control of cardiovascular disease (CVD) risk factors in 1,372 patients receiving medical care at two major urban medical centers in Brooklyn and Detroit. Information was extracted from charts of outpatient clinics.RESULTS -Of 1,372 active clinic patients with diabetes and hypertension, 1,247 (90.9%) had type 2 diabetes, and 26.7% met the target blood pressure of 130/85 mmHg. A total of 35.5% met the goal LDL cholesterol level of Ͻ100 mg/dl, 26.7% had an HbA 1c Ͻ7%, and 45.6% were on antiplatelet therapy. Only 3.2% of patients met the combined ADA goal for BP, LDL cholesterol, and HbA 1c .CONCLUSIONS -Optimal control of CVD risk factors in adults with diabetes was achieved only in a minority of patients. Results reflect the inherent difficulties in achieving these complex guidelines in our present health care systems. Diabetes Care 25:718 -723, 2002

OBJECTIVE -Associated with insulin resistance in type 2 diabetes are increased serum triglycerides, decreased HDL cholesterol, and a predominance of large VLDL, small LDL, and small HDL particles. The comparative effects of thiazolidinedione insulin sensitizers on serum lipoprotein particle concentrations and sizes in type 2 diabetes are not known. We studied the effects of pioglitazone (PIO) and rosiglitazone (ROSI) treatments on serum lipoprotein particle concentrations and sizes in type 2 diabetic patients with dyslipidemia. RESEARCH DESIGN AND METHODS-This is a prospective, randomized, doubleblind, multicenter, parallel-group study. After a 4-week placebo washout period, patients randomized to PIO (n ϭ 369) were treated with 30 mg q.d. for 12 weeks followed by 45 mg q.d. for another 12 weeks, while patients randomized to ROSI (n ϭ 366) were treated with 4 mg q.d. followed by 4 mg b.i.d. for the same intervals. Lipoprotein subclass particle concentrations and sizes were determined by proton nuclear magnetic resonance spectroscopy at baseline and end point (PIO [n ϭ 333] and ROSI [n ϭ 325] patients).RESULTS -PIO treatment increased total VLDL particle concentration less than ROSI treatment and decreased VLDL particle size more than ROSI. PIO treatment reduced total LDL particle concentration, whereas ROSI treatment increased it. Both treatments increased LDL particle size, with PIO treatment having a greater effect. Whereas PIO treatment increased total HDL particle concentration and size, ROSI treatment decreased them; both increased HDL cholesterol levels.CONCLUSIONS -PIO and ROSI treatments have different effects on serum lipoprotein subclass particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia.

Background Insulin is the most effective drug available to achieve glycaemic goals in patients with type 2 diabetes. Yet, there is reluctance among physicians, specifically primary care physicians (PCPs) in the USA, to initiate insulin therapy in these patients. Aims To describe PCPs’ attitudes about the initiation of insulin in patients with type 2 diabetes and identify areas in which there is a clear lack of consensus. Methods Primary care physicians practicing in the USA, seeing 10 or more patients with type 2 diabetes per week, and having > 3 years of clinical practice were surveyed via an internet site. The survey was developed through literature review, qualitative study and expert panel. Results Primary care physicians ( n = 505, mean age = 46 years, 81% male, 62% with > 10 years practice; 52% internal medicine) showed greatest consensus on attitudes regarding risk/benefits of insulin therapy, positive experiences of patients on insulin and patient fears or concerns about initiating insulin. Clear lack of consensus was seen in attitudes about the metabolic effects of insulin, need for insulin therapy, adequacy of self-monitoring blood glucose, time needed for training and potential for hypoglycaemia in elderly patients. Conclusions The beliefs of some PCPs are inconsistent with their diabetes treatment goals (HbA1c ≤ 7%). Continuing medical education programmes that focus on increasing primary care physician knowledge about the progression of diabetes, the physiological effects of insulin, and tools for successfully initiating insulin in patients with type 2 diabetes are needed. Disclosures Drs Hayes and Jacober are employees and stockholders of Eli Lilly and Company. Dr Fitzgerald is a consultant to Eli Lilly and Company. What's known Insulin is the most effective drug available to achieve glycaemic goals in patients with type 2 diabetes, yet there is reluctance among many physicians to initiate insulin therapy in these patients. Diabetes specialists tend to be more aggressive than primary care physicians (PCPs) with insulin initiation in patients with type 2 diabetes, and US physicians are more disposed to delay insulin than physicians in other countries. What's new This article confirms that US PCPs lack consensus on some beliefs about insulin initiation. Consensus was seen regarding insulin risk/benefits, positive patient experiences of insulin and patient fears about initiating insulin. No consensus was seen regarding insulin's metabolic effects, need for insulin, adequacy of self-monitoring blood glucose, time needed for training and potential for hypoglycaemia in elderly patients. Some PCPs have beliefs inconsistent with their diabetes treatment goals (HbA1c ≤ 7%).