Impact on glycated haemoglobin of a biological response-based measure of medication adherence.

AIMS: The aim of this study was to examine the relationship between a specific glycated haemoglobin (HbA1c) measurement and a pharmaceutical dispensings-based measure of adherence calculated over the 90 days before each HbA1c measure among patients who have newly initiated metformin therapy. METHODS: We identified 3109 people with type 2 diabetes who initiated metformin as their first-ever antihyperglycaemic drug, analysing all 9918 HbA1c measurements that were taken over the next 2 years. We used an adaptation of the 'proportion of days covered' method for assessing medication adherence that corresponded to an ∼90-day interval preceding an HbA1c measurement, terming the adaptation the 'biological response-based proportion of days covered' (BRB-PDC). To account for multiple observations per patient, we analysed the association between HbA1c and BRB-PDC within the generalized estimating equation framework. Analyses were stratified by HbA1c level before metformin initiation using a threshold of 8% (64 mmol/mol). RESULTS: After multivariable adjustment using 0% adherence as the reference category, BRB-PDC in the range 50-79% was associated with HbA1c values lower by -0.113 [95% confidence interval (CI) -0.202, -0.025] among patients with pre-metformin HbA1c <8%, and by -0.247 (95% CI -0.390, -0.104) among those with HbA1c ≥8% at metformin initiation. Full adherence (≥80%) was associated with HbA1c values lower by -0.175% (95% CI -0.257, -0.093) and by -0.453% (95% CI -0.586, -0.320). CONCLUSIONS: Using this novel short-interval approach that more closely associates adherence with the expected biological response, the association between better adherence and HbA1c levels was considerably stronger than has been previously reported; however, the strength of the impact was dependent upon the HbA1c level before initiating metformin.

Cardiovascular disease, heart failure, chronic kidney disease and depression independently increase the risk of incident diabetes.

AIMS/HYPOTHESIS: Diabetes increases the risk of cardiovascular disease (CVD) and heart failure, as well as other serious complications, such as renal disease and depression. However, these conditions are often present prior to diabetes diagnosis. We sought to determine whether they increase the risk of developing diabetes independent of other risk factors. METHODS: We identified 58,056 non-diabetic adults aged ≥30 years with no evidence of diabetes. Using electronic medical records, we identified the presence of four conditions at baseline (CVD, heart failure, renal disease and depression) and then estimated diabetes incidence over 5 years separately for patients with and without each of these conditions. Each incidence estimate was adjusted for baseline values of age, sex, fasting glucose, body mass index, systolic blood pressure, triacylglycerol, HDL-cholesterol, smoking and the presence of the other three conditions. RESULTS: Patients with CVD were 35% (95% CI 23-48%) more likely to develop diabetes after controlling for other risk factors. Heart failure was independently associated with an increase in diabetes incidence of 48% (95% CI 27-73%), and depression was associated with a 10% (95% CI 2-20%) increase. Chronic kidney disease was associated with a non-significant risk increase of 10% (95% CI -2-25%). CONCLUSIONS/INTERPRETATION: Complications of diabetes are more prevalent among patients who will ultimately develop diabetes, and increase the risk of diabetes independently of other known risk factors. The apparent bidirectional relationships suggest that primary prevention of CVD may also help prevent diabetes.

Risk of chronic kidney disease in hypertensive patients with other metabolic conditions.

Using a retrospective cohort design and electronic medical records, we examined chronic kidney disease (CKD) risk over a 6-year period among hypertensive patients in relation to the presence of diabetes, hyperlipidaemia and/or high body mass index. After adjusting for age, sex, smoking status and baseline glomerular filtration rate (GFR), hypertensive patients without other metabolic risk factors had a relative risk of CKD (versus normotensive patients) of 2.0 (95% CI 1.8-2.2); hypertensive patients with other metabolic conditions had adjusted relative risks ranging from 2.4 to 2.6 for those without comorbid diabetes, and from 3.3 to 5.5 for those with comorbid diabetes. Our study thus confirms prior research demonstrating elevated CKD risk in hypertensive patients, and suggests that this risk varies substantially in relation to other metabolic conditions, especially diabetes.

Type 2 diabetes: incremental medical care costs during the 8 years preceding diagnosis.

OBJECTIVE: To describe and analyze medical care costs for the 8 years preceding a diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS: From electronic records of a large group-model health maintenance organization (HMO), we ascertained the medical care costs preceding diagnosis for all members with type 2 diabetes who were newly diagnosed between 1988 and 1995. To isolate incremental costs (costs caused by the future diagnosis of diabetes), we subtracted the costs of individually age- and sex-matched HMO members without impending diabetes from the costs of members who were destined to receive this diagnosis. We also compared these prediagnosis costs with the first 3 years of postdiagnosis costs. RESULTS: An economic burden from impending diabetes is apparent for at least 8 years before diagnosis, beginning with costs for outpatient and pharmacy services. Diabetes-associated incremental costs (costs of type 2 diabetic patients minus matched costs of nondiabetic patients) averaged $1,205 per type 2 diabetic patient per year during the first eight prediagnostic years, including $1,913 each year for the 3 years preceding diagnosis. In the year immediately preceding diagnosis, incremental costs were equivalent to those observed in the second and third years after diagnosis. CONCLUSIONS: Incremental costs of diabetes begin at least 8 years before diagnosis and grow at an accelerating rate as diagnosis approaches and immediately after diagnosis. These incremental costs span the full range of medical services. Furthermore, the majority of these costs are for conditions not normally associated with diabetes or its complications.

Predictors of glycemic control in insulin-using adults with type 2 diabetes.

OBJECTIVE: To determine the characteristics that influence glycemic control among insulin-using adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied all 1,333 eligible members of a large not-for-profit health maintenance organization who responded to a 1997 survey. We tested associations among demographic, treatment, and psychometric variables with mean 1997 HbA1c values. The Problem Areas in Diabetes (PAID) instrument was used to assess the emotional effect of living with diabetes, and the Short Form 12 Physical Function Scale was used to assess the effect of physical limitations on daily activities. Based on differences between and within treatment groups, we built models to predict glycemic control for subgroups of subjects who were using insulin alone and those who were using insulin in combination with an oral hypoglycemic agent. RESULTS: Younger age, lower BMI, and increased emotional distress about diabetes (according to the PAID scale) were all significant predictors (P < 0.05) of worse glycemic control. However, except among individuals with an HbA1c level of >8.0 who were receiving combination therapy, only approximately 10% of the variance in glycemic control could be predicted by demographic, treatment, or psychometric characteristics. CONCLUSIONS: Personal characteristics explain little of the variation in glycemic control in insulin-using adults with type 2 diabetes. Possible explanations are that the reduced complexity of control in type 2 diabetes makes the disease less sensitive to personal factors than control in type 1 diabetes, that health-related behavior is less driven by personal and environmental characteristics among older individuals, or that, in populations exposed to aggressive glycemic control with oral hypoglycemic agents and nurse care managers, personal differences become largely irrelevant.

Type 2 diabetes: incremental medical care costs during the first 8 years after diagnosis.

OBJECTIVE: To describe and analyze the time course of medical care costs caused by type 2 diabetes, from the time of diagnosis through the first 8 postdiagnostic years. RESEARCH DESIGN AND METHODS: From electronic health maintenance organization (HMO) records, we ascertained the ongoing medical care costs for all members with type 2 diabetes who were newly diagnosed between 1988 and 1995. To isolate incremental costs (costs caused by the diagnosis of diabetes), we subtracted the costs of individually matched HMO members without diabetes from costs of members with diabetes. RESULTS: The economic burden of diabetes is immediately apparent from the time of diagnosis. In year 1, total medical costs were 2.1 times higher for patients with diabetes compared with those without diabetes. Diabetes-associated incremental costs (type 2 diabetic costs minus matched costs for people without diabetes) averaged $2,257 per type 2 diabetic patient per year during the first 8 postdiagnostic years. Annual incremental costs varied relatively little over the period but were higher during years 1, 7, and 8 because of higher-cost hospitalizations for causes other than diabetes or its complications. CONCLUSIONS: For the first 8 years after diabetes diagnosis, patients with type 2 diabetes incurred substantially higher costs than matched nondiabetic patients, but those high costs remained largely flat. Once the growth in costs due to general aging is controlled for, it appears that diabetic complications do not increase incremental costs as early as is commonly believed. Additional research is needed to better understand how diabetes and its diagnosis affect medical care costs over longer periods of time.

Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors.

OBJECTIVE: To estimate the prevalence and incidence of congestive heart failure (CHF) in populations with and without type 2 diabetes and to identify risk factors for diabetes-associated CHF. RESEARCH DESIGN AND METHODS: We searched the inpatient and outpatient electronic medical records of 9,591 individuals diagnosed with type 2 diabetes before 1 January 1997 and those of an age- and sex-matched control group without diabetes for a diagnosis of CHF. Among those without a baseline diagnosis of CHF, we searched forward for 30 months for incident cases of CHF. We constructed multiple logistic regression models to identify risk factors for both prevalent and incident CHF. RESULTS: CHF was prevalent in 11.8% (n = 1,131) of diabetic subjects and 4.5% (n = 435) of control subjects at baseline. We observed incident cases of CHF in 7.7% of diabetic subjects free of CHF at baseline (650 of 8,460) and in 3.4% of control subjects (314 of 9,156). In diabetic subjects, age, diabetes duration, insulin use, ischemic heart disease, and elevated serum creatinine were independent risk factors for both prevalent and incident CHF. Better glycemic control at baseline, and improved glycemic and blood pressure control at follow-up predicted the development of CHF. CONCLUSIONS: Despite controlling for age, duration of diabetes, presence of ischemic heart disease, and presence of hypertension, insulin use was associated with both prevalent and incident CHF. Why insulin use and better glycemic control both at baseline and follow-up independently predicted CHF deserves further study.

Replicating the chronic disease score (CDS) from automated pharmacy data.

Michael Von Korff and colleagues at the Center for Health Studies, Group Health Cooperative (GHC) of Puget Sound created a measure of chronic disease status (CDS) using automated outpatient pharmacy data. They reported the measure appeared to provide a stable and valid measure of health status. The availability of such a measure could become a new tool for a variety of applications, including screening, resource allocation, and quality assurance. The measure was replicated for its reliability and construct and predictive validity in the KPNW membership using automated pharmacy data. Reliability and validity were tested using correlation and regression techniques. The CDS showed test-retest reliability over time. It showed construct validity with the RAND-36 instrument and the BSI-8 depression screener. It showed predictive validity with health care visits and hospitalizations. The results were similar to those at GHC. The findings indicated that the CDS can serve, with certain precautions, as a readily accessible low cost measure of health status.

Ten-year follow-up of antidiabetic drug use, nonadherence, and mortality in a defined population with type 2 diabetes mellitus.

Studies performed for drug registration provide little insight into the long-term use and effectiveness of drugs in "real world" populations and settings. To obtain such insight, we used 10 years of electronic medical-record data from Kaiser Permanente Northwest Division, a large, group-model health maintenance organization in the United States, to study drug transitions, lapses in drug therapy, and mortality among 693 persons with newly diagnosed type 2 diabetes mellitus in 1988. We also studied an equivalently defined cohort of 1071 persons with new diagnoses in 1994, for whom the availability of laboratory results via electronic data permitted additional analyses. Cumulative mortality in the 1988 cohort increased steadily to 207 of 571 patients (36%) by 1997 (year 10). In 1988, 548 of 693 patients (79%) received initial monotherapy with a sulfonylurea. Insulin use rose as the use of sulfonylureas declined. Over this period, 504 of 693 patients (73%) discontinued or added drug therapy. Eight percent to 10% of both sulfonylurea users and insulin users discontinued drug use during the study period. In the 1994 cohort, two thirds of the subjects who discontinued therapy and were tested for glycosylated hemoglobin (Hb A1c) (n = 86) maintained good-to-excellent glycemic control. However, 78 discontinuers (38%) were not tested for Hb A1c, and, among this subset, 32% failed to visit a primary care clinician. The results of this study suggest that 5% to 10% of persons with type 2 diabetes mellitus avoid contact with the medical care system. Avoidance persists for at least the first 10 years after diagnosis but is more common in the first year after diagnosis. In addition, secondary failure of sulfonylureas begins within 1 year of diagnosis and continues at a steady pace. Almost 80% of patients initially treated with sulfonylureas added or switched to metformin or insulin within 10 years of diagnosis.

Changing patterns of antidepressant use and costs in a health maintenance organisation.

This study examined changes in the utilisation and costs of different antidepressants, particularly the selective serotonin reuptake inhibitors (SSRIs), and changes in the use of mental health services in a US health maintenance organisation (HMO) over the 8-year period following the introduction of SSRIs. It was hypothesised that SSRIs would be used increasingly in this setting, and that SSRI users would show a pattern of mental health service utilisation that was indicative of more severe psychiatric illnesses or prior treatment failures. Both hypotheses were accepted. The use of antidepressants nearly tripled over the 8-year period, with SSRIs showing the largest increase; per capita antidepressant costs increased more than 10-fold, largely because of the high cost per unit of SSRIs. Estimated daily doses of SSRIs were largely within the recommended ranges, although the duration of use was short if their primary purpose was the treatment of depression. Incident (first-time) users of SSRIs, and patients who switched to SSRIs from other antidepressants, used more inpatient and outpatient mental health services than users of other antidepressants. Use of the psychiatric hospital among antidepressant users increased, then decreased back to its first year level, psychiatric hospital days appeared to decrease over time, and outpatient mental health visits increased. The inverse relationship between use of SSRIs and use of inpatient mental health services suggests the need for a cost-effectiveness analysis in this setting.

Health care costs associated with escalation of drug treatment in type 2 diabetes mellitus.

The cost of different intensities of therapy in HMO patients with type 2 diabetes mellitus was studied. Health care utilization data from 1995 were obtained for 12,200 registrants from the Kaiser Permanente Northwest Diabetes Registry who had type 2 diabetes mellitus. The data were used to determine costs associated with the escalation of antidiabetic therapies in persons with type 2 diabetes mellitus. The total annual costs (in 1993 dollars) associated with no drug therapy, a sulfonylurea only, metformin, a sulfonylurea plus insulin, and insulin alone were $4400, $4187, $4838, $8856, and $7365, respectively. Per patient total costs were higher for patients who had received antidiabetic therapy in 1995 or previously than for those who had not ($5303 versus $4365) and for patients who had received insulin therapy than for those who had not ($7379 versus $4117). Macrovascular complications accounted for 62-89% of the cost associated with inpatient treatment of diabetes-related complications. The total cost of treating patients with type 2 diabetes mellitus at an HMO increased as antidiabetic therapies escalated.

Risk of progression of nephropathy in a population-based sample with type 2 diabetes.

AIMS: Progression through stages of nephropathy has not been well described in a large, well-characterized, population-based study. Our aims were to describe the progression of nephropathy and identify characteristics associated with progression in a U.S. population-based sample. METHODS: We identified 10,290 members of a managed care organization who had hypertension and type 2 diabetes, a urine albumin-to-creatinine ratio (UACR) measurement in 2001-2003, and at least 2 follow-up UACRs. Progression of nephropathy was defined as progression to a higher stage of nephropathy than was present at baseline. RESULTS: At baseline, 57% had normoalbuminuria, 31% had microalbuminuria, and 12% had macroalbuminuria. The incidence of nephropathy progression (per 1000 person-years) was 94.7, 35.1, and 6.5 for normo-, micro-, and macro-albuminuria, respectively. ACEi/ARB use ranged from 61-67%, except among patients with macroalbuminuria at follow-up. Age, diabetes duration, and A1C were significant predictors of progression. CONCLUSIONS: Our study, one of the first to examine the progression of nephropathy in a U.S. population-based sample, showed that among adults with diabetes and hypertension, the burden of nephropathy and its progression may be greater than previously reported. Further, the use of ACEi/ARBs was not optimal.