BACKGROUND The metabolic defects of nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes mellitus (T2DM) seem to be specifically targeted by pioglitazone. However, information about its long-term use in this population is limited. OBJECTIVE To determine the efficacy and safety of long-term pioglitazone treatment in patients with NASH and prediabetes or T2DM. DESIGN Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT00994682). SETTING University hospital. PARTICIPANTS Patients (n = 101) with prediabetes or T2DM and biopsy-proven NASH were recruited from the general population and outpatient clinics. INTERVENTION All patients were prescribed a hypocaloric diet (500-kcal/d deficit from weight-maintaining caloric intake) and then randomly assigned to pioglitazone, 45 mg/d, or placebo for 18 months, followed by an 18-month open-label phase with pioglitazone treatment. MEASUREMENTS The primary outcome was a reduction of at least 2 points in the nonalcoholic fatty liver disease activity score in 2 histologic categories without worsening of fibrosis. Secondary outcomes included other histologic outcomes, hepatic triglyceride content measured by magnetic resonance and proton spectroscopy, and metabolic parameters. RESULTS Among patients randomly assigned to pioglitazone, 58% achieved the primary outcome (treatment difference, 41 percentage points [95% CI, 23 to 59 percentage points]) and 51% had resolution of NASH (treatment difference, 32 percentage points [CI, 13 to 51 percentage points]) (P < 0.001 for each). Pioglitazone treatment also was associated with improvement in individual histologic scores, including the fibrosis score (treatment difference, -0.5 [CI, -0.9 to 0.0]; P = 0.039); reduced hepatic triglyceride content from 19% to 7% (treatment difference, -7 percentage points [CI, -10 to -4 percentage points]; P < 0.001); and improved adipose tissue, hepatic, and muscle insulin sensitivity (P < 0.001 vs. placebo for all). All 18-month metabolic and histologic improvements persisted over 36 months of therapy. The overall rate of adverse events did not differ between groups, although weight gain was greater with pioglitazone (2.5 kg vs. placebo). LIMITATION Single-center study. CONCLUSION Long-term pioglitazone treatment is safe and effective in patients with prediabetes or T2DM and NASH. PRIMARY FUNDING SOURCE Burroughs Wellcome Fund and American Diabetes Association.

Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial

Long-term Effects of Lifestyle Intervention or Metformin on Diabetes Development and Microvascular Complications: the DPP Outcomes Study

Obesity and diabetes mellitus have reached epidemic proportions in the past few years. During 2011 to 2012, more than one-third of the US population was obese. Although recent trend data indicate that the epidemic has leveled off, prevalence of abdominal obesity continues to rise, especially among adults. As seen for obesity, the past few decades have seen a doubling of the diabetes mellitus incidence with an increasing number of type 2 diabetes mellitus cases being diagnosed in children. Significant racial and ethnic disparities exist in the prevalence and trends of obesity and diabetes mellitus. In general, in both adults and children, non-Hispanic blacks and Mexican Americans seem to be at a high risk than their non-Hispanic white counterparts. Secular changes in agricultural policies, diet, food environment, physical activity, and sleep have all contributed to the upward trends in the diabesity epidemic. Despite marginal improvements in physical activity and the US diet, the food environment has changed drastically to an obesogenic one with increased portion sizes and limited access to healthy food choices especially for disadvantaged populations. Interventions that improve the food environment are critical as both obesity and diabetes mellitus raise the risk of cardiovascular disease by ≈2-fold. Among those with type 2 diabetes mellitus, significant sex differences occur in the risk of cardiovascular disease such that diabetes mellitus completely eliminates or attenuates the advantages of being female. Given the substantial burden of obesity and diabetes mellitus, future research efforts should adopt a translational approach to find sustainable and holistic solutions in preventing these costly diseases.

Epidemiology of Obesity and Diabetes and Their Cardiovascular Complications.

At least 45% of patients with type 2 diabetes (T2D) fail to achieve adequate glycemic control (HbA1c <7%). One of the major contributing factors is poor medication adherence. Poor medication adherence in T2D is well documented to be very common and is associated with inadequate glycemic control; increased morbidity and mortality; and increased costs of outpatient care, emergency room visits, hospitalization, and managing complications of diabetes. Poor medication adherence is linked to key nonpatient factors (eg, lack of integrated care in many health care systems and clinical inertia among health care professionals), patient demographic factors (eg, young age, low education level, and low income level), critical patient beliefs about their medications (eg, perceived treatment inefficacy), and perceived patient burden regarding obtaining and taking their medications (eg, treatment complexity, out-of-pocket costs, and hypoglycemia). Specific barriers to medication adherence in T2D, especially those that are potentially modifiable, need to be more clearly identified; strategies that target poor adherence should focus on reducing medication burden and addressing negative medication beliefs of patients. Solutions to these problems would require behavioral innovations as well as new methods and modes of drug delivery.

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Poor medication adherence in type 2 diabetes: recognizing the scope of the problem and its key contributors

To forecast future trends in diabetes prevalence, morbidity, and costs in the United States, the Institute for Alternative Futures has updated its diabetes forecasting model and extended its projections to 2030 for the nation, all states, and several metropolitan areas. This paper describes the methodology and data sources for these diabetes forecasts and discusses key implications. In short, diabetes will remain a major health crisis in America, in spite of medical advances and prevention efforts. The prevalence of diabetes (type 2 diabetes and type 1 diabetes) will increase by 54% to more than 54.9 million Americans between 2015 and 2030; annual deaths attributed to diabetes will climb by 38% to 385,800; and total annual medical and societal costs related to diabetes will increase 53% to more than $622 billion by 2030. Improvements in management reducing the annual incidence of morbidities and premature deaths related to diabetes over this time period will result in diabetes patients living longer, but requiring many years of comprehensive management of multiple chronic diseases, resulting in dramatically increased costs. Aggressive population health measures, including increased availability of diabetes prevention programs, could help millions of adults prevent or delay the progression to type 2 diabetes, thereby helping turn around these dire projections.

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Diabetes 2030: Insights from Yesterday, Today, and Future Trends

OBJECTIVE To update estimates of the economic burden of undiagnosed diabetes, prediabetes, and gestational diabetes mellitus in 2012 in the U.S. and to present state-level estimates. Combined with published estimates for diagnosed diabetes, these statistics provide a detailed picture of the economic costs associated with elevated glucose levels. RESEARCH DESIGN AND METHODS This study estimated health care use and medical expenditures in excess of expected levels occurring in the absence of diabetes or prediabetes. Data sources that were analyzed include Optum medical claims for ∼4.9 million commercially insured patients who were continuously enrolled from 2010 to 2012, Medicare Standard Analytical Files containing medical claims for ∼2.6 million Medicare patients in 2011, and the 2010 Nationwide Inpatient Sample containing ∼7.8 million hospital discharge records. The indirect economic burden includes reduced labor force participation, missed workdays, and reduced productivity. State-level estimates reflect geographic variation in prevalence, risk factors, and prices. RESULTS The economic burden associated with diagnosed diabetes (all ages) and undiagnosed diabetes, gestational diabetes, and prediabetes (adults) exceeded $322 billion in 2012, consisting of $244 billion in excess medical costs and $78 billion in reduced productivity. Combined, this amounts to an economic burden exceeding $1,000 for each American in 2012. This national estimate is 48% higher than the $218 billion estimate for 2007. The burden per case averaged $10,970 for diagnosed diabetes, $5,800 for gestational diabetes, $4,030 for undiagnosed diabetes, and $510 for prediabetes. CONCLUSIONS These statistics underscore the importance of finding ways to reduce the burden of prediabetes and diabetes through prevention and treatment.

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The Economic Burden of Elevated Blood Glucose Levels in 2012: Diagnosed and Undiagnosed Diabetes, Gestational Diabetes Mellitus, and Prediabetes

Background Scope of practice (SOP) laws governing Certified Registered Nurse Anesthetists (CRNAs) vary by state and drive CRNA practice and reimbursement. Objective To test whether the odds of an anesthesia complication vary by SOP and delivery model (CRNA only, anesthesiologist only, or mixed anesthesiologist and CRNAs team). Methods Anesthesia claims and related complications were identified in a large commercial payor database, including inpatient and ambulatory settings. Logit regression models were estimated by setting to determine the impact of SOP and delivery model on the odds of an anesthesia-related complication, while controlling for patient characteristics, patient comorbidities, procedure and procedure complexity, and local area economic factors. Results Overall, 8 in every 10,000 anesthesia-related procedures had a complication. However, complications were 4 times more likely in the inpatient setting (20 per 10,000) than the outpatient setting (4 per 10,000). In both settings, the odds of a complication were found to differ significantly with patient characteristics, patient comorbidities, and the procedures being administered. The odds of an anesthesia-elated complication are particularly high for procedures related to childbirth. However, complication odds were not found to differ by SOP or delivery model. Conclusions Our research results suggest that there is strong evidence of differences in the likelihood of anesthesia complications by patient characteristics, patient comorbidities, and the procedures being administered, but virtually no evidence that the odds of a complication differ by SOP or delivery model.

Scope of Practice Laws and Anesthesia Complications: No Measurable Impact of Certified Registered Nurse Anesthetist Expanded Scope of Practice on Anesthesia-related Complications.

BACKGROUND: Medication nonadherence is an imperative public health concern. Among patients with type 2 diabetes mellitus (T2DM), poor adherence to antidiabetic agents is strongly associated with suboptimal glycemic control. Poor adherence and hyperglycemia greatly increase diabetes-related morbidity and mortality. At a national level, diabetes drug adherence using average proportion of days covered (PDC) is estimated to range between 36% and 81%, with an estimated range for diabetes control between 38% and 47%. At a state level no such studies exist. OBJECTIVE: To estimate the level of medication adherence to antidiabetic agents and of diabetes control, and their association among patients with T2DM receiving medication treatment at the state and the Metropolitan Statistical Area (MSA) levels among the populations covered by commercial insurance, Medicare, or Medicaid. METHODS: The study population included adults with T2DM aged ≥ 18 years who were identified using ICD-9-CM code 250.xx, who received diabe...

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Bo Pang

Papers

The Economic Burden of Elevated Blood Glucose Levels in 2012: Diagnosed and Undiagnosed Diabetes, Gestational Diabetes Mellitus, and Prediabetes

Scope of Practice Laws and Anesthesia Complications: No Measurable Impact of Certified Registered Nurse Anesthetist Expanded Scope of Practice on Anesthesia-related Complications.

Geographic Variation in Antidiabetic Agent Adherence and Glycemic Control Among Patients with Type 2 Diabetes