Roberta Harrison McDuffie

Determinants of Weight Gain in the Action to Control Cardiovascular Risk in Diabetes Trial

OBJECTIVE Identify determinants of weight gain in people with type 2 diabetes mellitus (T2DM) allocated to intensive versus standard glycemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS We studied determinants of weight gain over 2 years in 8,929 participants (4,425 intensive arm and 4,504 standard arm) with T2DM in the ACCORD trial. We used general linear models to examine the association between each baseline characteristic and weight change at the 2-year visit. We fit a linear regression of change in weight and A1C and used general linear models to examine the association between each medication at baseline and weight change at the 2-year visit, stratified by glycemia allocation. RESULTS There was significantly more weight gain in the intensive glycemia arm of the trial compared with the standard arm (3.0 ± 7.0 vs. 0.3 ± 6.3 kg). On multivariate analysis, younger age, male sex, Asian race, no smoking history, high A1C, baseline BMI of 25–35, high waist circumference, baseline insulin use, and baseline metformin use were independently associated with weight gain over 2 years. Reduction of A1C from baseline was consistently associated with weight gain only when baseline A1C was elevated. Medication usage accounted for <15% of the variability of weight change, with initiation of thiazolidinedione (TZD) use the most prominent factor. Intensive participants who never took insulin or a TZD had an average weight loss of 2.9 kg during the first 2 years of the trial. In contrast, intensive participants who had never previously used insulin or TZD but began this combination after enrolling in the ACCORD trial had a weight gain of 4.6–5.3 kg at 2 years. CONCLUSIONS Weight gain in ACCORD was greater with intensive than with standard treatment and generally associated with reduction of A1C from elevated baseline values. Initiation of TZD and/or insulin therapy was the most important medication-related factor associated with weight gain.

Evaluation of a Remote Monitoring System for Diabetes Control

PURPOSE The use of technology to implement cost-effective health care management on a large scale may be an alternative for diabetes management but needs to be evaluated in controlled trials. This study assessed the utility and cost-effectiveness of an automated Diabetes Remote Monitoring and Management System (DRMS) in glycemic control versus usual care. METHODS In this randomized, controlled study, patients with uncontrolled diabetes on insulin were randomized to use of the DRMS or usual care. Participants in both groups were followed up for 6 months and had 3 clinic visits at 0, 3, and 6 months. The DRMS used text messages or phone calls to remind patients to test their blood glucose and to report results via an automated system, with no human interaction unless a patient had severely high or low blood glucose. The DRMS made adjustments to insulin dose(s) based on validated algorithms. Participants reported medication adherence through the Morisky Medication Adherence Scale-8, and diabetes-specific quality of life through the diabetes Daily Quality of Life questionnaire. A cost-effectiveness analysis was conducted based on the estimated overall costs of DRMS and usual care. FINDINGS A total of 98 patients were enrolled (59 [60%] female; mean age, 59 years); 87 participants (89%) completed follow-up. HbA1c was similar between the DRMS and control groups at 3 months (7.60% vs 8.10%) and at 6 months (8.10% vs 7.90%). Changes from baseline to 6 months were not statistically significant for self-reported medication adherence and diabetes-specific quality of life, with the exception of the Daily Quality of Life-Social/Vocational Concerns subscale score (P = 0.04). IMPLICATIONS An automated system like the DRMS may improve glycemic control to the same degree as usual clinic care and may significantly improve the social/vocational aspects of quality of life. Cost-effectiveness analysis found DRMS to be cost-effective when compared to usual care and suggests DRMS has a good scale of economy for program scale up. Further research is needed to determine how to sustain the benefits seen with the automated system over longer periods.

Diabetes in clinical practice

Type 2 diabetes: the modern epidemic.- Management of diabetes.- Non-insulin agents in the management of type 2 diabetes.- Insulin in the management of type 2 diabetes.- Complications of diabetes.- Diabetic emergencies.- Patient education.

Factors associated with failure to achieve a glycated haemoglobin target of <8.0% in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial

The aim of this study was to identify the clinical features of participants in the standard therapy arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) glycaemia trial who failed to reach the glycated haemoglobin (HbA1c) target. We analysed 4685 participants in the standard therapy arm, comparing participants who reached the HbA1c target of <8.0% with those whose HbA1c level was ≥8.0% 12 months after randomization. Baseline and 12‐month clinical characteristics were compared. At 12 months after randomization, 3194 participants had HbA1c <8.0% and 1491 had HbA1c ≥8.0%. Black race [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.61–0.89; p = 0.002], severe hypoglycaemia (OR 0.57, CI 0.37–0.89; p = 0.014) and insulin use (OR 0.51, CI 0.40–0.65; p < 0.001) were associated with failure to reach HbA1c goal at 12 months in the adjusted model. Even with free medications, free visits with clinicians and aggressive titration of medications, >30% of participants in the standard arm of the ACCORD trial had an HbA1c ≥8.0% at 1 year. Participants who were black, had severe hypoglycaemia and were on insulin were more likely to have an above‐target HbA1c concentration after 12 months on the standard protocol.

Urinary Catalytic Iron in Patients with Type 2 Diabetes without Microalbuminuria—a Substudy of the ACCORD Trial

To the Editor: The presence of microalbuminuria in patients with diabetes mellitus (DM)1 is associated with a 3- to 5-fold higher risk of cardiovascular mortality than in patients with DM without microalbuminuria and a risk of progression to end-stage kidney disease that is 10-fold higher. Predicting and/or preventing the development of albuminuria have substantial potential to improve outcomes and reduce costs in patients with DM. Catalytic iron, also known as labile iron, consists of chemical forms that can participate in redox cycling. This property makes catalytic iron potentially hazardous because it can participate in the generation of powerful oxidant species, such as hydroxyl radicals and/or reactive iron–oxygen complexes such as the ferryl or perferryl ion (1, 2). Animal models of glomerular disease exhibit increased urinary catalytic iron, and administration of an iron chelator reduces concentrations and protects against proteinuria (3). These findings suggest a pathogenetic role for catalytic iron. We postulated that the concentrations of catalytic iron may be higher in patients with DM, and if that is so, higher concentrations could precede the occurrence of proteinuria. We conducted an ancillary study in a subgroup of 9 clinical centers (in 2 networks from the southeastern and western regions of the US) of the NIH-sponsored ACCORD (Action to Control Cardiovascular Risk in Diabetes) Trial (4) to determine the prevalence of increased catalytic iron in participants with nonpathologic renal function and the absence of microalbuminuria (<30 …

Type 2 diabetes: the modern epidemic

Type 2 diabetes is a major clinical and public health problem. It is estimated that in the year 2000, 171 million people worldwide had type 2 diabetes, including about 18 million Americans, and it is estimated that these numbers will grow to 366 million people worldwide and 30 million Americans by the year 2030.

Complications of diabetes

Microvascular complications are specific for diabetes and are almost certainly related to hyperglycemia (see Figure 5.1). Hyperglycemia leads to multiple biochemical changes, some of which are listed in Figure 5.2, that cause tissue damage [1, 2]. These lead to changes in various organs as summarized in Figure 5.1. Most of these changes can be prevented by good glycemic control which prevents the development of the complications and slows their progression [3].

Insulin in the management of type 2 diabetes

Insulin is the most the effective available medication for treating hyperglycemia in type 2 diabetes. If used appropriately, it can decrease any level of elevated A1C to, or close to, the desired goal. This chapter begins with a presentation of indications for insulin therapy in type 2 diabetes. Normal physiological insulin patterns will be reviewed, highlighting how awareness of these patterns can guide the development of insulin treatment regimens. The next section will provide an overview of the characteristics of available insulin preparations. The chapter will end with a discussion of potential strategies for initiating and advancing insulin therapy.

Management of diabetes

Historically, patient treatment has been reactive, guided by the assessment of patients’ symptoms. However, elevated blood glucose, elevated blood pressure and elevated cholesterol often have no symptoms. Yet, research has demonstrated that early and successful treatment of these problems can prevent or delay complications of diabetes [1].

Non-insulin agents in the management of type 2 diabetes

Eight different classes of medication, in addition to insulin, are currently approved for treatment of hyperglycemia in type 2 diabetes. Beneficial effects of antihyperglycemic agents appear to be mediated predominantly through their ability to lower blood glucose. Studies are currently in progress to determine whether any particular agent (or treatment strategy) has specific advantages, beyond glucose lowering, in terms of reducing cardiovascular endpoints [1, 2].