Hypoglycaemia is reduced with use of inhaled Technosphere® Insulin relative to insulin aspart in type 1 diabetes mellitus.

AIM: To evaluate the effect of final HbA1c levels on the incidences of hypoglycaemia in participants with type 1 diabetes treated with inhaled Technosphere® Insulin or subcutaneous insulin aspart, reported in alignment with the International Hypoglycaemia Study Group recommendations. METHODS: In the randomized, phase 3, multicentre AFFINITY-1 study, adults (N = 375) who had type 1 diabetes for ≥ 12 months and an HbA1c level of 58-86 mmol/mol (7.5-10.0%) were randomized to receive basal insulin plus either inhaled Technosphere Insulin or subcutaneous insulin aspart. This was a post-hoc regression analysis on a subset (N = 279) of the randomized AFFINITY-1 cohort for whom baseline and end-of-treatment HbA1c values were reported. Primary outcome measures were incidence and event rates for levels 1, 2 and 3 hypoglycaemia, respectively defined as blood glucose levels of ≤ 3.9 mmol/l, < 3.0 mmol/l or requiring external assistance for recovery. RESULTS: Participants treated with Technosphere Insulin experienced statistically significantly fewer level 1 and 2 hypoglycaemic events and a lower incidence of level 3 hypoglycaemia than participants treated with insulin aspart. The lower rate of hypoglycaemia with Technosphere Insulin was observed across the range of end-of-treatment HbA1c levels. Technosphere Insulin was associated with higher rates of hypoglycaemia 30-60 min after meals, but significantly lower rates 2-6 h after meals. CONCLUSIONS: Participants using Technosphere Insulin experienced clinically non-inferior glycaemic control and lower hypoglycaemia rates across a range of HbA1c levels compared with participants receiving insulin aspart. ClinicalTrials.gov: NCT01445951.

Improvement in glycated haemoglobin evaluated by baseline body mass index: a meta-analysis of the liraglutide phase III clinical trial programme.

In the liraglutide clinical trial programme, liraglutide 1.2 and 1.8 mg were found to effectively lower glycated haemoglobin (HbA1c) in patients with type 2 diabetes (T2D). It is unknown whether baseline body mass index (BMI) is a predictor of change in HbA1c observed during a clinical trial with liraglutide or placebo treatment. The present meta-analysis of patient-level data, using pooled data from seven phase III trials [LEAD-1-6 and the liraglutide versus sitagliptin trial (LIRA-DPP-4)] for liraglutide 1.2, 1.8 mg and placebo (n = 3222), identified no significant correlation between baseline BMI (<20 kg/m(2) up to 45 kg/m(2) ) and HbA1c reduction for placebo or liraglutide 1.2 mg, and a modest, clinically non-relevant, association for liraglutide 1.8 mg [-0.010 (95% confidence interval -0.020, -0.001)], whereby a 10 kg/m(2) increase in baseline BMI corresponded to 0.10%-point (1.1 mmol/mol) greater HbA1c reduction. In summary, reductions in HbA1c obtained during clinical trials with liraglutide or placebo treatment were independent of baseline BMI.

Progression to insulin therapy among patients with type 2 diabetes treated with sitagliptin or sulphonylurea plus metformin dual therapy.

AIM: To assess time to insulin initiation among patients with type 2 diabetes mellitus (T2DM) treated with sitagliptin versus sulphonylurea as add-on to metformin. METHODS: This retrospective cohort study used GE Centricity electronic medical records and included patients aged ≥18 years with continuous medical records and an initial prescription of sitagliptin or sulphonylurea (index date) with metformin for ≥90 days during 2006-2013. Sitagliptin and sulphonylurea users were matched 1 : 1 using propensity score matching, and differences in insulin initiation were assessed using Kaplan-Meier curves and Cox regression. We used conditional logistic regression to examine the likelihood of insulin use 1-6 years after the index date for each year. RESULTS: Propensity score matching produced 3864 matched pairs. Kaplan-Meier analysis showed that sitagliptin users had a lower risk of insulin initiation compared with sulphonylurea users (p = 0.003), with 26.6% of sitagliptin users initiating insulin versus 34.1% of sulphonylurea users over 6 years. This finding remained significant after adjusting for baseline characteristics (hazard ratio 0.76, 95% confidence interval 0.65-0.90). Conditional logistic regression analyses confirmed that sitagliptin users were less likely to initiate insulin compared with sulphonylurea users [odds ratios for years 1-6: 0.77, 0.79, 0.81, 0.57, 0.29 and 0.75, respectively (p < 0.05 for years 4 and 5)]. CONCLUSIONS: In this real-world matched cohort study, patients with T2DM treated with sitagliptin had a significantly lower risk of insulin initiation compared with patients treated with sulphonylurea, both as add-on to metformin.

Comparison of liraglutide versus other incretin-related anti-hyperglycaemic agents.

The two classes of incretin-related therapies, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have become important treatment options for patients with type 2 diabetes. Sitagliptin, saxagliptin, vildagliptin and linagliptin, the available DPP-4 inhibitors, are oral medications, whereas the GLP-1 RAs-twice-daily exenatide, once-weekly exenatide and once-daily liraglutide-are administered subcutaneously. By influencing levels of GLP-1 receptor stimulation, these medications lower plasma glucose levels in a glucose-dependent manner with low risk of hypoglycaemia, affecting postprandial plasma glucose more than most other anti-hyperglycaemic medications. Use of GLP-1 RAs has been shown to result in greater glycaemic improvements than DPP-4 inhibitors, probably because of higher levels of GLP-1 receptor activation. GLP-1 RAs can also produce significant weight loss and may reduce blood pressure and have beneficial effects on other cardiovascular risk factors. Although both classes are well tolerated, DPP-4 inhibitors may be associated with infections and headaches, whereas GLP-1 RAs are often associated with gastrointestinal disorders, primarily nausea. Pancreatitis has been reported with both DPP-4 inhibitors and GLP-1 RAs, but a causal relationship between use of incretin-based therapies and pancreatitis has not been established. In clinical trials, liraglutide has shown efficacy and tolerability and resulted in certain significant benefits when compared with exenatide and sitagliptin.

Experimental observation of asymmetrical microwave jets and far-field distribution generated by a dual-material system.

In this paper, we report the experimental and numerical investigation of plane wave diffraction by an all-dielectric dual-material cuboid. Edge diffraction by a cuboid leads to the generation of a narrow, high intensity beam in the near-field region called a photonic jet. We examine the dependence of the jet behavior and orientation on the materials and dimensions of constitutive parts in the microwave frequency domain. The possibility to shift and deviate the resultant microwave jet in the near-field region of such a structure depending on the size of constitutive parts is demonstrated numerically. Experimentally, we observe a shift in the spatial position of the jet. The experimental asymmetric electric field profile observed in the far-field region is attributed to the input of multiple edge waves generated by the dual-material cuboid. The presented results may be scaled at different frequency bands such as optical frequencies for designing nanostructures enabling the focusing and deviation functionality and creation of new optical devices which would satisfy the needs of emerging nanophotonic applications.

Patient-reported outcomes following treatment with the human GLP-1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes.

AIM: As weight gain and hypoglycaemia associated with glimepiride therapy can negatively impact weight perceptions, psychological well-being and overall quality of life in type 2 diabetes, we investigated whether liraglutide treatment could improve these factors. METHODS: Seven hundred and thirty-two patients with type 2 diabetes completed a 77-item questionnaire during a randomized, 52-week, double-blind study with liraglutide 1.2 mg (n = 245) or 1.8 mg (n = 242) compared with glimepiride 8 mg (n = 245). RESULTS: Mean (SE) decreases in glycated haemoglobin levels were greater with liraglutide 1.2 mg [-0.84 (0.08)%] and 1.8 mg [-1.14 (0.08)%] than glimepiride [-0.51 (0.08)%; p = 0.0014 and p < 0.0001, respectively]. Patients gained weight on glimepiride [mean (SE), 1.12 (0.27) kg] but lost weight on liraglutide [1.2 mg: -2.05 (0.28) kg; 1.8 mg: -2.45 (0.28) kg; both p < 0.0001]. Patient weight assessment was more favourable with liraglutide 1.8 mg [mean (SE) score: 40.0 (2.0)] than glimepiride [48.7 (2.0); p = 0.002], and liraglutide 1.8 mg patients were 52% less likely to feel overweight [odds ratio (OR) 0.48; 95% confidence interval (CI): 0.331-0.696]. Mean (SE) weight concerns were less with liraglutide [1.2 mg: 30.0 (1.2); 1.8 mg: 32.8 (1.2)] than glimepiride [38.8 (1.2); p < 0.0001 and p < 0.001, respectively], with liraglutide groups 45% less likely to report weight concern (OR 0.55, 95% CI: 0.41-0.73). Mean (SE) mental and emotional health and general perceived health improved more with liraglutide 1.8 mg [476.1 (2.8) and 444.2 (3.2), respectively] than glimepiride [466.3 (2.8) and 434.5 (3.2), respectively; p = 0.012 and p = 0.033, respectively]. CONCLUSIONS: Improved glycaemic control and decreased weight with liraglutide 1.8 mg vs. glimepiride can improve psychological and emotional well-being and health perceptions by reducing anxiety and worry associated with weight gain.

The safety and efficacy of liraglutide with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1-5 studies.

Liraglutide is a new glucagon-like peptide-1 (GLP-1) receptor agonist and a true GLP-1 analogue. After successful phase 2 studies, liraglutide was assessed in a series of phase 3 trials [(Liraglutide Effect and Action in Diabetes (LEAD)] designed to demonstrate efficacy and safety across the continuum of type 2 diabetes antihyperglycaemic care, both as monotherapy and in combination with commonly used oral antidiabetic drugs (OADs). The LEAD programme also compared liraglutide with other OADs. As a monotherapy, liraglutide demonstrated significant improvements in glycaemic control in comparison with glimepiride. When combined with one or two OADs, reductions in haemoglobin A1c, fasting plasma glucose and postprandial glucose were generally greater with liraglutide than with comparators. Throughout the trials, liraglutide was associated with weight reduction; in most instances, the reduction from baseline was significantly greater than that seen with comparators. Improvements in assessments of beta-cell function were consistently shown with liraglutide treatment across all trials. Furthermore, reductions in systolic blood pressure were reported. Liraglutide was associated with a low risk of hypoglycaemia and was generally well tolerated. The majority of adverse effects were gastrointestinal, the most frequent of which was nausea.

Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets - the TITRATE study.

AIMS: To compare efficacy and safety of two fasting plasma glucose (FPG) titration targets [4.4-6.1 mmol/l (80-110 mg/dl) and 3.9-5.0 mmol/l (70-90 mg/dl)] using a patient-directed, treat-to-target algorithm for once-daily basal insulin in insulin-naïve subjects with type 2 diabetes suboptimally treated with oral antidiabetes drugs (OADs). METHODS: In this 20-week, randomized, controlled, open-label, multicentre, treat-to-target study, 244 insulin-naïve subjects with type 2 diabetes, HbA(1c)>or=7.0 and

Comparison of vildagliptin and thiazolidinedione as add-on therapy in patients inadequately controlled with metformin: results of the GALIANT trial--a primary care, type 2 diabetes study.

AIM: To assess the efficacy and tolerability of vildagliptin compared with thiazolidinediones (TZDs) as an add on to metformin treatment in a primary care patient population with type 2 diabetes. METHODS: This was a randomized, 12-week, open-label study comparing vildagliptin (100 mg, n = 1653) and TZD (agent and dose at the investigators' discretion, n = 825) add-on therapy in patients inadequately controlled [haemoglobin A(1C) (HbA(1c)): 7-10%] on a stable dose of metformin (> or =1000 mg/day). The primary objective was to test non-inferiority of vildagliptin to TZDs for the difference in change in HbA(1c) from baseline [established if the upper limit of the two-sided 95% confidence intervals (CI) did not exceed 0.4%]. RESULTS: Mean (+/- s.e.) change in HbA(1c) from baseline to study endpoint was -0.68 +/- 0.02% in the vildagliptin group and -0.57 +/- 0.03% in the TZD group. The difference between groups was -0.11% (95% CI: -0.17% and -0.04%), establishing the non-inferiority of vildagliptin (p = 0.001) after 3 months of treatment. Vildagliptin was non-inferior to TZDs for subgroups of race, age and body mass index. Body weight increased in the TZD group (0.33 +/- 0.11 kg) and decreased in the vildagliptin group (mean: -0.58 +/- 0.09 kg; p < 0.001 for difference). Adverse events occurred in similar proportions of patients in both groups (vildagliptin: 39.5% and TZD: 36.3%) Hypoglycaemia and abnormal changes in liver enzymes were uncommon. CONCLUSIONS: This short-term study suggests that vildagliptin is as effective as TZDs after 3-month treatment as an add-on to metformin in a primary care population that included diverse patient subgroups.

The effect of the availability of inhaled insulin on glycaemic control in patients with Type 2 diabetes failing on oral therapy: the evaluation of Exubera as a therapeutic option on insulin initiation and improvement in glycaemic control in clinical practice (EXPERIENCE) trial.

AIM: To examine the impact of inhaled human insulin (Exubera, EXU) on patient or physician willingness to adopt insulin after oral glucose-lowering agent failure. METHODS: During a randomized controlled trial in primary, secondary and tertiary care in Europe and North America, 739 patients using >or= 2 oral glucose-lowering agents with glycated haemoglobin (HbA(1c)) >or= 8.0% were assigned to two treatment groups: Group 1 (standard care with the option of EXU) or Group 2 (standard care only). Standard care included adjusting oral therapy (optimizing current regimen or adding/omitting agents) and/or initiating subcutaneous (s.c.) insulin. The primary endpoint was difference in HbA(1c) between randomized groups at 26 weeks. Secondary outcomes included differences in the rate of uptake of insulin therapy, proportion achieving satisfactory glycaemic control, treatment satisfaction and safety outcomes. RESULTS: At baseline, insulin was initiated by more [odds ratio 6.0; 95% confidence interval (CI) 4.2 to 8.8; P < 0.0001] patients in Group 1 (86.2%; 76.7% EXU plus 9.5% s.c.) than Group 2 (50.7%; s.c. insulin only). At 26 weeks, mean (sd) changes in HbA(1c) from baseline were -2.0% (1.2%) and -1.7% (1.3%) in Groups 1 and 2, respectively, a difference of -0.2% (95% CI: -0.1% to -0.4%; P = 0.004). In Group 1, 45% of patients achieved an HbA(1c)

Plasma clearance rates and renal clearance of 3H-labeled cyclic AMP and 3H-labeled cyclic GMP in the dog.

Previously, in an attempt to understand the mechanisms involved in the regulation of plasma cyclic nucleotides, we measured concentrations of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in plasma from selected blood vessels of anesthetized dogs. The observation that the renal venous plasma concentrations of both cyclic nucleotides were less than arterial concentrations suggested that the kidney might be an important site for the elimination of these compounds from plasma and prompted further investigation of the renal handling of these compounds. Tracer doses of either [(3)H]cAMP or [(3)H]cGMP were administered to anesthetized dogs by constant intravenous infusion, and metabolic clearance rates were determined. Concentrations of endogenous cyclic nucleotide and of cyclic nucleotide radioactivity were measured in aortic and renal venous plasma as well as in urine. Renal venous plasma [(3)H]cGMP was 39% and [(3)H]cAMP was 65% of the concentration in arterial plasma. Endogenous cyclic nucleotide levels showed a similar relationship. The plasma clearance rates (PCR) were 271+/-27 ml/min (mean+/-SE) for cGMP and 261+/-17 for cAMP. The total kidney clearance (calculated as the renal plasma flow x renal cyclic nucleotide extraction ratio) accounted for 52+/-4% and 30+/-2% of the PCR for cGMP and cAMP, respectively. Only about two-thirds of the total kidney clearance of each cyclic nucleotide could be accounted for by urinary excretion, the remainder presumably being the result of renal metabolism. The urinary clearances of (3)H-labeled cGMP (40.9+/-4.2 ml/min) and endogenous cGMP (45.0+/-2.3 ml/min) were not significantly different from each other. Both were approximately 50% greater than the glomerular filtration rate, which was 27.1+/-2.0 ml/min, indicating that a significant amount of urinary cGMP is derived from plasma by tubular secretion. In contrast, the urinary clearances of (3)H-labeled cAMP (23.7+/-1.9 ml/min) and endogenous cAMP (27.2+/-2.6 ml/min) were nearly equal both to each other and to the glomerular filtration rate, which was 24.6+/-1.7 ml/min. Thus, in the dog, glomerular filtration of plasma cAMP appears to be responsible for most of the cAMP found in urine. Renla production of cAMP, which in humans contributes from a third to a half of the urinary cAMP, was quantitatively of minor importance in the dog.Thus, under the conditions of these experiments in dogs, renal elimination appears to be responsible for half of the PCR of cGMP and about a third of the PCR of cAMP. About a third of the renal elimination of both cyclic nucleotides appears to be due to metabolic degradation within the kidney, and the balance is due to excretion in the urine.

Sources of cyclic nucleotides in plasma.

In order to determine the sites of net production and removal of the cyclic nucleotides in plasma, various blood vessels were catheterized in 17 anesthetized dogs and arterial and venous concentrations of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) were measured by radioimmunoassay. Aortic cAMP was 30+/-2 nM (mean+/-SE) and cGMP was 13+/-1 nM. There were no significant differences for either cyclic nucleotide between the concentration in the aorta and that in the inferior vena cava, coronary sinus, hepatic vein, and femoral vein. The concentration of cAMP in renal venous plasma was 25% lower than in aortic plasma, and renal venous cGMP was 51% lower than in the aorta. The pulmonary arterial concentrations of cAMP and cGMP were slightly lower than in the aorta. The concentration of cGMP in the superior mesenteric vein plasma was 83% greater than in aortic plasma; the concentration of cAMP in this vessel was only 16% greater than that in the aorta. Superior vena cava concentrations of both cyclic nucleotides were slightly greater than arterial concentrations. THE RESULTS SUGGEST THAT: (a) the kidneys are a major site of removal of both cyclic nucleotides from plasma. (b) The lungs may be a site of net addition of both cyclic nucleotides to plasma. (c) The small intestine is a site of net production of both cyclic nucleotides, particularly cGMP. (d) The liver probably removes cyclic nucleotides from plasma. (e) Since no other organs or regions studied added detectable net amounts of cyclic nucleotides to plasma, and since the turnover of these compounds in plasma is known to be rapid, the production of plasma cyclic nucleotides under basal conditions may well be the result of small net contributions may well be the result of small net contributions from many tissues or bidirectional fluxes between tissues and plasma, or both.

Partnering with governments and other institutions: driving change in diabetes care.

The human and material cost of type 2 diabetes is a cause of increasing concern for health professionals, representative organisations and governments worldwide. The scale of morbidity and mortality has led the United Nations to issue a resolution on diabetes, calling for national policies for prevention, treatment and care. There is clearly an urgent need for a concerted response from all interested parties at the community, national and international level to work towards the goals of the resolution and create effective, sustainable treatment models, care systems and prevention strategies. Action requires both a 'bottom-up' approach of public awareness campaigns and pressure from healthcare professionals, coupled with a 'top-down' drive for change, via partnerships with governments, third sector (non-governmental) organisations and other institutions. In this review, we examine how existing collaborative initiatives serve as examples for those seeking to implement change in health policy and practice in the quest to alleviate the health and economic burden of diabetes. Efforts are underway to provide continuous and comprehensive care models for those who already have type 2 diabetes; in some cases, national plans extend to prevention strategies in attempts to improve overall public health. In the spirit of partnership, collaborations with governments that incorporate sustainability, long-term goals and a holistic approach continue to be a driving force for change. It is now critical to maintain this momentum and use the growing body of compelling evidence to educate, inform and deliver a long-term, lasting impact on patient and public health worldwide.

Long-term cholesterol-lowering effects of psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia.

BACKGROUND: Hypercholesterolemia is a major risk factor for coronary heart disease and nutrition management is the initial therapeutic approach. OBJECTIVE: This multicenter study evaluated the long-term effectiveness of psyllium husk fiber as an adjunct to diet in the treatment of persons with primary hypercholesterolemia. DESIGN: Men and women with hypercholesterolemia were recruited. After following an American Heart Association Step I diet for 8 wk (dietary adaptation phase), eligible subjects with serum LDL-cholesterol concentrations between 3.36 and 4.91 mmol/L were randomly assigned to receive either 5.1 g psyllium or a cellulose placebo twice daily for 26 wk while continuing diet therapy. RESULTS: Serum total and LDL-cholesterol concentrations were 4.7% and 6.7% lower in the psyllium group than in the placebo group after 24-26 wk (P < 0.001). Other outcome measures did not differ significantly between groups. CONCLUSIONS: Treatment with 5.1 g psyllium twice daily produces significant net reductions in serum total and LDL-cholesterol concentrations in men and women with primary hypercholesterolemia. Psyllium therapy is an effective adjunct to diet therapy and may provide an alternative to drug therapy for some patients.

Bone scan patterns of patients with diffuse metastatic carcinoma of the axial skeleton.

Bone scan findings (using 99mTc-stannous pyrophosphate) in five patients with diffuse metastatic carcinoma of the axial skeleton are reviewed. Although there were few visually recognizable asymmetries of tracer localization, the diffuse involvement was diagnosed through abnormally elevated counting rates in the axial skeleton, decreased visualization of the kidneys, and faint or absent visualization of the appendicular skeleton.

Classification of diabetes mellitus.

Diabetes mellitus affects almost 16 million Americans. It has become a major public health problem and the number one cause of adult blindness, end-stage renal disease, and nontraumatic amputations in the United States. It also markedly increases the risk for cardiovascular, cerebrovascular, and peripheral artery disease. The resultant increased morbidity and mortality results in a cost from diabetes of almost $100 billion annually in the United States. Studies like the UK Prospective Diabetes Study have noted that a substantial percentage of patients with newly diagnosed diabetes already have evidence of microvascular and macrovascular complications of the disease. This indicates that diabetes began in these individuals many years before it was diagnosed. By reducing the diagnostic glycemic threshold for diabetes and recommending regular screening of individuals at increased risk, the ADA hopes that patients will have diabetes diagnosed earlier, before the occurrence of complications and at a time when appropriate treatment can reduce the long-term complications, adverse clinical outcomes, and impaired quality of life that today afflict so many diabetic individuals.

Defining and measuring quality of diabetes care.

The literature on diabetes mellitus has increasingly focused on the quality of diabetes care and its measurement. Serious and widespread quality problems exist throughout American medicine. Current efforts to improve will not succeed unless we undertake a major, systematic effort to overhaul how we deliver health care services, educate and train clinicians, and assess and improve quality. This article defines the components of quality of diabetes care provision and discusses approaches to their measurement individually and globally.

High-density lipoprotein cholesterol. Recommendations for routine testing and treatment.

Evidence from epidemiologic, lipid intervention, and coronary angiographic studies demonstrates the importance of high-density lipoprotein cholesterol (HDL-C) in coronary artery disease (CAD) risk. Data from these studies strongly support the measurement of HDL-C in all patients screened for CAD. Patients with low levels should be treated using nonpharmacologic measures. High-risk patients deserve consideration for specific drug treatment.

Management of type 2 diabetes: update on new pharmacological options.

The value of intensive control of blood glucose levels has been clearly established. Data from the UKPDS demonstrated that improving glycemic control will reduce the risk of microvascular complications of type 2 diabetes, such as diabetic retinopathy, nephropathy, and peripheral neuropathy. Further, the metformin study in overweight patients and the epidemiological analysis of the study both demonstrated a reduction in macrovascular complications and mortality related to improved glycemic control. These findings should enhance awareness among both patients and physicians of the dangers of uncontrolled hyperglycemia and the need for early diagnosis and aggressive treatment for patients with type 2 diabetes. Optimal management of type 2 diabetes most often requires a combination of glucose-lowering medications to achieve glycemic control. Current guidelines for combination therapy advise the use of agents with differing and complementary mechanisms of action in order to maximize therapeutic activity and reduce toxicity. Earlier introduction of combination therapy is increasingly being recommended. The new glyburide/metformin combination medication may facilitate earlier, more appropriate and more effective treatment for patients with type 2 diabetes.

Disease management approaches to type 2 diabetes.

Diabetes is a serious and costly disorder. The economic impact on the health care delivery system in the United States is extremely large, and the cost to individual affected patients in terms of health status, productivity, and quality of life is immeasurable. Population-based DM initiatives are undergoing extensive testing and application. These strategies have been demonstrated to enhance the care delivered to diabetic patients, improve clinical outcomes and quality of life, and reduce the financial toll of managing the disease. These gains are very valuable to the MCO, which is concerned with providing optimal cost-effective patient care in a systematic fashion.