Salsalate improves glycemic control in patients with newly diagnosed type 2 diabetes

Chronic inflammation contributes to insulin resistance and type 2 diabetes mellitus (T2DM). We investigated whether treatment with salsalate, an anti-inflammatory medication, improves glycemia in a group of newly diagnosed drug-naïve patients with T2DM. The study was a randomized, double-blind, placebo-controlled trial. Diagnosis of T2DM was made within 2 months of enrollment, and participants had not received any anti-glycemic agent. Sixty adults were randomized to receive salsalate (3 g/day) or placebo for 12 weeks. Fasting plasma glucose and insulin, glucose 2 h after 75 g oral glucose, HbA1C, lipid profile, HOMA-IR, and HOMA-B were determined before and after treatment. Salsalate reduced fasting glucose from 6.3 ± 0.2 mmol/l to 5.4 ± 0.2 mmol/l (P < 0.01) and TG from 1.9 ± 0.2 mmol/l to 1.5 ± 0.2 mmol/l (P < 0.03). Fasting insulin levels were increased in the salsalate group from 18.8 ± 1.6 to 21.6 ± 3.9, while they decreased in the placebo group. HbA1c rose in the placebo group from 6.2% ± 0.2 to 7.9% ± 1.1 mmol/mol, but decreased in the intervention group from 6.1% ± 0.5 to 5.6% ± 0.2 mmol/mol (P < 0.04 for between-group comparison). HOMA-IR did not change but HOMA-B increased ~1.7-fold (P = 0.06) in the salsalate group. The results show that salsalate is effective in improving glycemic control in newly diagnosed naïve patients with T2DM. The optimal duration of treatment with salsalate and sustainability of its effect requires further study (IRCT138709011465N1).     

Short-term intensive glycemic control improves vibratory sensation in type 2 diabetes

Strict long-term glycemic control has been reported to prevent or improve diabetic peripheral neuropathy, but the effects of short-term glycemic control have not been clarified in patients with type 2 diabetes. To investigate reversibility of impaired vibratory sensation by short-term glycemic control, we used the TM31 liminometer and C64 tuning fork methods to measure peripheral neuropathy. Thirty-one type 2 diabetes patients with poor glycemic control (HbA1c: 10.8+/-0.4%, mean+/-S.E.M., range from 7.9% to 16.2%) were administered strict glycemic control. Vibratory sensation before and after short-term glycemic control was evaluated, and the metabolic profile including plasma glucose, HbA1c, total cholesterol, HDL cholesterol, triglyceride, and free fatty acid (FFA) was measured. After 20.0+/-2.1 days of strict glycemic control, vibratory sensation improved significantly in both upper and lower extremities, assessed by TM31 liminometer and C64 tuning fork. Along with the improved glycemic control, lipid metabolism (total cholesterol, triglyceride and FFA) was significantly improved. Thus, short-term intensive glycemic control can improve vibratory sensation, metabolic changes in glucose and lipid metabolism being the factors responsible for improved of peripheral nerve function.     

Association between vitamin D status and glycemic profile in postmenopausal women with type 2 diabetes

The aim of this study is to evaluate the association between vitamin D status and glycemic profile in postmenopausal women with type 2 diabetes. A cross-sectional study was carried out with 70 (59.47 ± 6.47 years; 1.56 ± 0.05 m; 73.56 ± 13.01 kg; 30.30 ± 5.00 BMI kg/m²) postmenopausal women with type 2 diabetes (T2D). The blood samples were collected after fasting for 12 h and the main outcome parameters were serum follicle-stimulating hormone (FSH), estradiol; 25-OH vitamin D; insulin; C-Reactive Protein; cholesterol total (CT), triglycerides (TG), high density lipoprotein (HDL-cholesterol), glucose; calcium, HDL-cholesterol. The average serum 25(OH)D level in this study was 28.45 ± 8.26 ng/mL. The prevalence of hypovitaminosis D was 60%. Table 1 displays mean and standard deviation values for participants’ characteristics. The postmenopause status of the women studied was confirmed by FSH and estradiol measurement. All the clinical and anthropometric characteristics did not show difference (p > 0.05) between the groups (Table 2). Triglycerides level was highest (p < 0.0391) in the hypovitaminosis D group. The other serum markers did not show statistical differences (p > 0.05) between the groups. In conclusion, our results suggest that only TG level shows a negative correlation with vitamin D status in postmenopausal women with type 2 diabetes.     

Conjugated estrogen administration improves common carotid artery elastic properties in normotensive postmenopausal women

BACKGROUND: Various vascular effects of estrogens have been proposed to explain further the beneficial effect of replacement therapy in cardiovascular events. HYPOTHESIS: The study was undertaken to assess the effect of conjugated estrogen on the elastic properties of the large arteries in normotensive, healthy, postmenopausal women. METHODS: Toward this end, we investigated the acute effect of conjugated estrogen on the elastic properties of the common carotid artery (CCA) in 20 normotensive, healthy, postmenopausal women (age 54+/-3 years) at baseline and 20 min after the intravenous administration of 1.25 mg conjugated estrogens. The CCA distensibility was derived by a combination of surface ultrasonographic data and simultaneous blood pressure measurements at the brachial artery. The carotid pulsatility index, a measure of brain impedance, was determined electronically by tracing the CCA Doppler waveform. RESULTS: At baseline, CCA distensibility had a negative correlation with both patients' age and time since menopause (r = -0.57 and r = -0.48, p < 0.05 for both cases). After estrogen administration, estradiol and estrone plasma levels were restored to the range of usual premenopausal values. Estrogen induced a significant increase in CCA distensibility by 0.92+/-0.005 dyne(-1) x cm2 x 10(-6) (from 2.03 to 2.95 dyne(-1) x cm2 x 10(-6)) and a significant reduction in CCA pulsatility index by 0.24+/-0.06, (from 2.17 to 1.93) (p < 0.001 for both cases). The improvement in CCA distensibility had a negative correlation with both patients' age and time since menopause (r= -0.46 and r = -0.44, respectively, p < 0.05 for both cases). CONCLUSIONS: Acute conjugated estrogen administration induced an improvement in CCA elasticity and a reduction in brain impedance in normotensive, postmenopausal women. As the age of women and the time since menopause increased, the improvement in carotid distensibility decreased in such selected subjects.     

Sitagliptin added to voglibose monotherapy improves glycemic control in patients with type 2 diabetes

Aims/Introduction

Type 2 diabetes mellitus is a progressive disease that frequently requires patients to use more than one oral antihyperglycemic agent to achieve adequate glycemic control. The present multicenter, randomized study assessed the efficacy and safety of the addition of sitagliptin to ongoing voglibose monotherapy (0.2–0.3 mg three times daily) in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control (glycated hemoglobin ≥6.9% and <10.5%).

Materials and Methods

The present study had an initial 12‐week, double‐blind treatment period in which patients were randomized (1:1) to sitagliptin 50 mg/day (n = 70) or placebo (n = 63), followed by a 40‐week, open‐label treatment period during which all patients received sitagliptin 50 mg/day, that could have been increased to 100 mg/day for patients meeting predefined glycemic criteria.

Results

After 12 weeks, treatment with sitagliptin resulted in placebo‐subtracted mean changes from baseline in glycated hemoglobin (the primary end‐point), fasting plasma glucose and 2‐h postmeal glucose of –0.9%, –22.5 mg/dL and –51.3 mg/dL, respectively (all, P < 0.001). During the double‐blind period, adverse experiences were reported with similar frequency in both treatment groups, and the occurrences of hypoglycemia and gastrointestinal adverse experiences were low. In the open‐label period, sustained improvements in glycemic parameters were observed with sitagliptin treatment, and sitagliptin was generally well tolerated.

Conclusions

Sitagliptin added on to ongoing voglibose monotherapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control. This trial was registered with ClinicalTrails.gov (no. NCT00837577).     

Combined aerobic and resistance exercise improves glycemic control and fitness in type 2 diabetes

We investigated the effect of an 8 week circuit training (CT) program, combining aerobic and resistance exercise, on indices of glycemic control, cardiorespiratory fitness, muscular strength and body composition in 16 subjects (age 52 +/- 2 years) with type 2 diabetes using a prospective randomised crossover protocol. Submaximal exercise heart rate and rate pressure product were significantly lower after training (P<0.05), whilst ventilatory threshold increased (11.8 +/- 0.7 vs 13.8 +/- 0.6 ml kg(-1)min(-1), P<0.001). Muscular strength also increased with training (403 +/- 30 to 456 +/- 31 kg, P<0.001), whilst skinfolds (148.7 +/- 11.5 vs 141.1 +/- 10.7 mm, P<0.05), % body fat (29.5 +/- 1.0 vs 28.7 +/- 1.1%, P<0.05) and waist:hip ratio (99.2 +/- 1.5 vs 97.9 +/- 1.4%, P<0.05) significantly decreased. Concurrently, peak oxygen uptake (P<0.05) and exercise test duration (P<0.001) increased following training, whilst glycated hemoglobin (P<0.05) and fasting blood glucose (P<0.05) decreased. CT is an effective method of training that improved functional capacity, lean body mass, strength and glycemic control in subjects with type 2 diabetes.     

Comorbidity and glycemic control in patients with type 2 diabetes

BACKGROUND: It is commonly believed that good glycemic control is hard to achieve in patients with diabetes mellitus and concurrent chronic illnesses. OBJECTIVE: To determine the impact of comorbidity on glycemic control at presentation and subsequent follow-up in patients with type 2 diabetes. METHODS: We studied 654 consecutive patients who presented to a diabetes clinic in 1997. Comorbidity was rated using the Chronic Disease Score (CDS) index, which is a validated, weighted score that takes into account the patient's age, sex, and classes of medications. Univariate and multivariate linear regressions were used to determine the contribution of age, body mass index (calculated as weight in kilograms divided by the square of height in meters), diabetes duration, type of therapy, and CDS to initial hemoglobin A(1c) (HbA(1c)) level. A similar analysis was performed for the 169 patients with follow-up HbA(1c) levels 6 months after presentation. RESULTS: Patients were 90% African American, and 66% female, with average age of 53 years. Average diabetes duration was 5 years; body mass index, 33; HbA(1c) level, 8.8%; and CDS, 1121 (range, 232-7953). At presentation, patients with higher CDSs tended to be older and to have a lower HbA(1c) level, but multivariate linear regression showed that receiving pharmacological therapy, younger age, and having a lower C-peptide level were the only significant contributors to HbA(1c) level. In the 169 follow-up patients, presenting characteristics were not significantly different from those of the full cohort: average initial HbA(1c) level was 8.8%; CDS, 1073. Their HbA(1c) level at 6 months averaged 7.5% and the CDS had no significant impact on their follow-up HbA(1c) level. CONCLUSION: Comorbidity does not appear to limit achievement of good glycemic control in patients with type 2 diabetes.     

Repaglinide improves blood glucose control in sulphonylurea-naive type 2 diabetes

The prandial glucose regulator repaglinide has a rapid onset of action, a short half-life and is metabolised mainly by the liver. Here we report the findings of a 10-week, double-blind, parallel, placebo controlled, randomised trial with repaglinide in 25 diet-treated, sulphonylurea-na?ve patients with Type 2 diabetes. Repaglinide was titrated, based on capillary blood glucose, from 0.5 mg to a maximum of 4 mg, preprandially with breakfast and dinner. After 10 weeks, repaglinide was associated with a decrease in HbA(1c) of 2.3%Hb relative to the placebo group (P=0.018). This reflected a 30% decrease within the repaglinide group from a mean HbA(1c) of 7.0 to 4.9%Hb (P<0.002). Repaglinide was also associated with a decrease in fructosamine, by 0.88 mmol/l, relative to placebo (P<0.001), with a 20% decrease (from 3.80 to 3.04 mmol/l) within the repaglinide group (P<0.001). Fasting and postprandial blood glucose concentrations decreased in association with repaglinide by 3.6 and 6.4 mmol/l, respectively, relative to placebo (P<0.001 in each case). Within the repaglinide group fasting and postprandial blood glucose decreased by 3.9 and 6.2 mmol/l, respectively (P<0.001 in each case). The number of patients reporting hypoglycaemia in the repaglinide group was similar to placebo (15 vs. 20, respectively; NS). Test meal assessments confirmed that repaglinide effectively controls glucose levels by stimulating mealtime insulin secretion. Fasting serum insulin concentration was not raised compared to baseline or placebo during repaglinide therapy, albeit that fasting glucose levels were decreased by repaglinide. Twice-daily meal-related insulin secretagogue therapy with repaglinide, a new short and rapid-acting prandial glucose regulator, is capable of improving all measures of glycaemic control without increased hypoglycaemia or fasting hyperinsulinaemia.     

Synchronous provider visit and self-management education improves glycemic control in Hispanic patients with long-standing type 2 diabetes

PURPOSE: The purpose of this study was to evaluate the efficacy of a multidisciplinary diabetes self-management program. The study focused on improving diabetes control by synchronizing regularly scheduled provider visits with a multidisciplinary diabetes education program. This intervention was instituted in Hispanic patients with long-standing poorly controlled type 2 diabetes. METHODS: The study was initiated as a performance improvement project. A group of 44 type 2 diabetes patients followed by the internal medicine faculty with HbA1c levels greater than 9.5 over a 12-month period was identified. Twenty-three of the identified patients were enrolled in a synchronous care group. A cohort control group of the remaining 21 patients not participating in the intervention was followed with routine care. The intervention group shared similar demographic characteristics, medication regimens, initial diabetes control, and a number of provider visits with the control group. The primary outcome of interest for the study is the HbA1c level. RESULTS: The findings demonstrated that our synchronous management approach significantly improved HbA1c level over standard management for medically indigent Hispanic patients with long-standing poorly controlled type 2 diabetes (P < .001). The majority of the patients (89%) in the Intensive Management Group had declines in HbA1c level from baseline, compared to the Standard Management Group (60%, P = .04). CONCLUSION: The temporal linkage between routine provider visits and a diabetes self-management education intervention in poorly controlled Hispanic patients with long-standing type 2 diabetes led to a significant improvement in HbA1c levels.     

Combined estrogen replacement therapy on metabolic control in postmenopausal women with diabetes mellitus

Previous studies have shown that the incidence of diabetes is higher when women come to menopause. This study was carried out to examine the effects of combined estrogen replacement therapy (ERT) on diabetes in postmenopausal women. PubMed/MEDLINE was searched for English-language articles published between January 1997 and June 2011. Studies that examined ERT on the incidence of diabetes and randomized clinical trials that evaluated combined ERT (estrogen plus progesterone) on diabetic indices in postmenopausal women were included. Pooled relative risks were calculated using a random- or a fixed-effects model. Sixteen studies comprising 17,971 cases were included. Based on the pooled data, ERT significantly reduced the incidence of diabetes [odds ratio (OR), 0.61; 95% confidence interval (CI), 0.55–0.68, ERT past/current/continuous use vs. never use; OR, 0.57; 95% CI, 0.51–0.65, ERT current/continuous use vs. past/never use]. Women with combined ERT have significantly lower levels of fasting plasma glucose (mean difference, –1.41 mM/L; 95% CI, –2.49 to ?0.33 mM/L) and HbA1c (mean difference, –0.73%; 95% CI, from ?1.28 to ?0.18%) compared with placebo. Furthermore, combined ERT dramatically reduced plasma total cholesterol (mean difference, –0.34 mM/L; 95% CI, from ?0.53 to ?0.15 mM/L) and low-density lipoprotein (mean difference, –0.43 mM/L; 95% CI, from ?0.71 to ?0.14 mM/L) but slightly increased high-density lipoprotein (mean difference, 0.02 mM/L; 95% CI, from ?0.07 to 0.12 mM/L) levels as compared with placebo control. This systemic review and meta-analysis provides evidence that postmenopausal women taking low-dose combined ERT have a decreased risk of developing diabetes and have better diabetic control.     

Disordered glycemic control in women with type 2 diabetes is associated with increased TNF receptor-2 levels

BackgroundEvidence implicates tumor necrosis factor (TNF) in the pathophysiology of Type 2 Diabetes (T2D) through unclear mechanisms. We hypothesized that disordered glycemic control leads to TNF activation and increases in soluble-TNF (sTNF) and its receptors-1 (sTNFR1) and -2 (sTNFR2).MethodsWe characterized 265 T2D and non-diabetic Latin American subjects and assessed the relationship between the TNF system and fasting plasma glucose (FPG), hemoglobin-A1C (A1C), insulin (FPI), C-peptide and HOMA-Beta.ResultssTNF and sTNFR2 but not sTNFR1 levels were higher in T2D than non-diabetics (P < 0.0001). In T2D, sTNFR2 was associated with A1C and C-peptide (R² = 0.354, b = 0.504, P < 0.0001; b = 0.167, P = 0.049). Also, T2D patients with disordered glycemic control had increased sTNFR2 levels that correlated with FPG (Rho:0.393, P < 0.001), A1C (Rho:0.451, P < 0.001) and HOMA-Beta (Rho:-0.308, P = 0.005); events not observed in T2D patients with adequate glycemic control. Furthermore, sex-based comparative analyses of T2D patients showed that women compared to men had higher sTNFR2 levels (P = 0.017) that correlated with FPG, A1C, FPI and HOMA-Beta.ConclusionsDisordered glycemic control is associated with sTNF and sTNFR2. sTNFR2 levels were higher in T2D women than men. Thus, increased sTNFR2 levels may be an important biomarker for disordered glucose and inflammatory complications in T2D patients and women in particular.     

Raloxifene does not affect insulin sensitivity or glycemic control in postmenopausal women with type 2 diabetes mellitus: a randomized clinical trial.

Little is known about the metabolic or cardiovascular effects of selective ER modulators (SERMs), such as raloxifene hydrochloride (RLX), in postmenopausal women with type 2 diabetes mellitus (DM). Therefore, the effect of RLX vs. placebo (PL) on glycemic control, insulin sensitivity, as well as effects on a number of hormone, lipid, coagulation, and safety factors were determined in 30 postmenopausal women with type 2 DM in a randomized, double blind, cross-over trial. All participants had a SHBG serum concentration below 60 nmol/liter at baseline and had stable diabetes controlled by either oral hypoglycemic agents or diet for 1 month. In the first treatment period, participants received 12 wk of either PL or RLX, followed by an 8-wk washout before the second treatment period. In the second treatment period, participants were crossed over to the other treatment. Compared with PL, RLX did not significantly affect fasting blood glucose, hemoglobin A(1c), lipids, fasting insulin, or insulin sensitivity (as measured by the euglycemic clamp technique). Compared with PL, RLX reduced fibrinogen levels by 0.77 g/liter (P < 0.001), IGF-I by 2.4 nmol/liter (P < 0.001), and free T by 0.73 pmol/liter (P = 0.038) and increased SHBG by 5.5 nmol/liter (P = 0.001) and IGF-binding protein-3 by 0.57 ng/ml (P = 0.007). Our results demonstrate that RLX does not significantly affect glycemic control and has favorable or neutral effects on selected surrogate markers of cardiovascular risk in postmenopausal women with type 2 diabetes mellitus while decreasing hyperandrogenicity in these patients.     

Saxagliptin improves glycemic control by modulating postprandial glucagon and C-peptide levels in Chinese patients with type 2 diabetes

Aims

Saxagliptin reduced glycated hemoglobin (HbA_1c), fasting plasma glucose (FPG), and postprandial glucose (PPG) in Asian patients with type 2 diabetes mellitus (T2DM). To understand the physiology of this effect, indices of α- and β-cell function were measured in a subpopulation of Chinese patients following a noodle mixed-meal tolerance test.

Methods

Data from Chinese patients were pooled from two phase 3, 24-week studies of saxagliptin 5 mg/d as monotherapy in drug-naive patients and as add-on to metformin in patients inadequately controlled with metformin alone. The end points for β- and α-cell function were change from baseline in C-peptide, insulin, and glucagon areas under the curve from 0 to 180 min (AUC_0–180), insulinogenic index, and insulin sensitivity from Matsuda index after a mixed meal. Also glycemic variables, HbA_1c, FPG, and PPG (AUC_0–180), and homeostasis model assessment (HOMA) 2β were measured.

Results

At 24 weeks, greater improvements in adjusted mean change from baseline HbA_1c (difference vs placebo [95% CI], −0.33% [−0.50%, −0.17%], [−4 (−5.5, −1.9) mmol/mol], P < 0.0001), FPG (−0.41 [−0.78, −0.03] mmol/L, P = 0.03), PPG AUC_0–180 (−168 [−245, −91.8] mmol min/L, P < 0.0001), C-peptide AUC_0–180 (19.7 [5.2, 34.2] nmol min/L, P = 0.008), insulinogenic index (0.06% [0.02%, 0.09%], P = 0.002), and greater suppression of glucagon secretion (glucagon AUC_0–180, −322 [−493.6, −150.7] pmol min/L, P = 0.0003) were observed with saxagliptin versus placebo.

Conclusion

In Chinese patients with T2DM, saxagliptin as monotherapy or as add-on to metformin improved glycemic control by modulating α- and β-cell function.     

Telemedical care reduces hypoglycemias and improves glycemic control in children and adolescents with type 1 diabetes

Education programs for intensive insulin therapy were found to be valuable in improving glycemic control, but, due to low prevalence of type 1 diabetes in children and adolescents, access to those programs varies considerably in rural areas. We report on a telemedical care program that overcomes geographical isolation of patients on intensive insulin therapy. Sixty-one children and adolescents under the age of 26 participated in a telemedical care program. They stored daily information on blood glucose, injected insulin, meals and exercise in a glucosemeter with electronic memory and transferred the data via modem go a remote diabetes center outside of the region. By individual telephone consultations from home, they reviewed the data with a diabetologist at the diabetes center and adjusted their intensive insulin therapy in order to achieve predefined treatment goals. Patients were trained for 19 (6-48) weeks in the program and measured blood glucose 4.9 (1.7-4.9) times daily. Compared to the run-in-period, mean blood glucose had decreased (167 to 158 mg/dL, p < 0.01), standard deviation of blood glucose had decreased (81 to 70 mg/dL, p < 0.001), and frequency of hypoglycemia had decreased (5.2 to 3.3 in 4 weeks, p = 0.01) at the end of the program. The proportion of blood glucose values within the target range (80-180 mg/dL) had increased (47-55%, p < 0.001). HbAlc was reduced by 0.4% (-3.8 to +2.2%, p < 0.05). Telemedical care for intensive insulin therapy is safe, can improve glycemic control, and reduce the number of hypoglycemias in children and adolescents with type 1 diabetes.     

Achieving glycemic control in patients with type 2 diabetes and renal impairment

Defining optimal regimens for the management of diabetes among patients with renal impairment is often clinically challenging, and guidance on the optimal management of these patients in clinical practice can vary considerably. Moreover, as many anti-diabetes agents are predominantly excreted renally, treatment options to control blood glucose levels are limited for patients with type 2 diabetes and concomitant chronic kidney disease. Many of the widely used and more established anti-diabetes drugs cannot be used in this population either or must be down-titrated to reduce the increased risk of severe hypoglycemic episodes. A number of more recently available anti-diabetes drugs are indicated for use in patients with type 2 diabetes and chronic kidney disease. Newer drugs that may improve the currently very limited treatment options for patients with type 2 diabetes and renal impairment include the glucagon-like peptide-1 receptor agonists and the dipeptidyl peptidase-4 inhibitors. This review paper, based on a literature search for both original and review articles (Medline), relevant clinical practice/regulatory guidelines and integrating our own knowledge of the field, provides an up-to-date examination of the current treatment options available. However, further studies with larger populations of patients with type 2 diabetes and chronic kidney disease are needed to clarify the efficacy and safety of the different treatment options, including newer drugs.     

Insulin glargine-based therapy improves glycemic control in patients with type 2 diabetes sub-optimally controlled on premixed insulin therapies

The AT.LANTUS trial recently demonstrated the efficacy and safety of insulin glargine initiation and maintenance using two different treatment algorithms in poorly controlled type 2 diabetes mellitus (T2DM). This sub-analysis investigated glycemic control and safety in 686 patients switching from premixed insulin (premix) with or without (+/-OADs) to once-daily glargine (+/-OADs/prandial insulin). A 24-week, multinational (n=59), multicenter (n=611), randomized study comparing two algorithms (Algorithm 1: clinic-driven titration; Algorithm 2: patient-driven titration) in four glargine+/-OADs treatment groups: alone, once- (OD), twice- (BD) or >twice- (>BD) daily prandial insulin. After switching to the glargine regimen, HbA(1c) levels significantly improved in the overall group (9.0+/-1.3 to 8.0+/-1.2%; p<0.001) and in all subgroups; fasting blood glucose levels also improved in all subgroups (overall: 167.1+/-50.0 to 106.9+/-27.2 mg/dL [9.3+/-2.8 to 5.9+/-1.5 mmol/L]; p<0.001). The incidence of severe hypoglycemia was also low in all four subgroups (< or =1.7%). Patients with T2DM switching from premix+/-OADs to glargine+/-OADs had significant reductions in glycemic control with a low incidence of severe hypoglycemia. The addition of prandial (OD, BD or >BD) insulin was associated with further improvements in glycemic control. These data provide support for the stepwise introduction of prandial insulin to a more physiologic basal-bolus regimen, which is under investigation.