Changes in Glitazone Use Among Office-Based Physicians in the U.S., 2003�C2009

OBJECTIVE

Little is known regarding recent changes in glitazone use.

RESEARCH DESIGN AND METHODS

Interrupted time series analyses of nationally representative office-visit data using IMS Health''s National Disease and Therapeutic Index.

RESULTS

From 2003 through 2005, glitazone use increased steadily. From February 2005 to January 2007, rosiglitazone use decreased by 16% (95% CI −20 to −11) annually; pioglitazone use increased at an annual rate of 14% (9–18). During a period of Food and Drug Administration (FDA) advisories, rosiglitazone use declined sharply from 0.42 million monthly treatment visits (February 2007) to 0.13 million monthly visits (May 2008). Pioglitazone use remained stable, accounting for ∼5.8 million physician visits (77% of all glitazone use) where a treatment was used during the final 12 months of observation.

CONCLUSIONS

The combined effect of scientific publications, advisories, and media exposure was associated with a substantial decrease in rosiglitazone use. Despite a class-level FDA advisory, pioglitazone use was not similarly affected.Diabetes treatments change and evolve, and glitazones were rapidly incorporated into practice, with U.S. expenditures reaching $4.2 billion in 2007 (1). Even early evidence suggested rare but serious adverse cardiovascular events with glitazone use (2). Based on accumulating evidence (3), in May 2007 the Food and Drug Administration (FDA) issued an advisory about rosiglitazone''s cardiovascular risks (4,5), followed by a class-wide advisory in August 2007 and an additional rosiglitazone advisory in November 2007 (4).Emerging scientific evidence and the FDA advisories received considerable media coverage, and each of these factors may have been influential in affecting pioglitazone and rosiglitazone use. We examine pioglitazone and rosiglitazone use based on a nationally representative audit of office-based physicians.     

Full Accounting of Diabetes and Pre-Diabetes in the U.S. Population in 1988�C1994 and 2005�C2006

OBJECTIVE—We examined the prevalences of diagnosed diabetes, and undiagnosed diabetes and pre-diabetes using fasting and 2-h oral glucose tolerance test values, in the U.S. during 2005–2006. We then compared the prevalences of these conditions with those in 1988–1994.RESEARCH DESIGN AND METHODS—In 2005–2006, the National Health and Nutrition Examination Survey included a probability sample of 7,267 people aged ≥12 years. Participants were classified according to glycemic status by interview for diagnosed diabetes and by fasting and 2-h glucoses measured in subsamples.RESULTS—In 2005–2006, the crude prevalence of total diabetes in people aged ≥20 years was 12.9%, of which ∼40% was undiagnosed. In people aged ≥20 years, the crude prevalence of impaired fasting glucose was 25.7% and of impaired glucose tolerance was 13.8%, with almost 30% having either. Over 40% of individuals had diabetes or pre-diabetes. Almost one-third of the elderly had diabetes, and three-quarters had diabetes or pre-diabetes. Compared with non-Hispanic whites, age- and sex-standardized prevalence of diagnosed diabetes was approximately twice as high in non-Hispanic blacks (P < 0.0001) and Mexican Americans (P = 0.0001), whereas undiagnosed diabetes was not higher. Crude prevalence of diagnosed diabetes in people aged ≥20 years rose from 5.1% in 1988–1994 to 7.7% in 2005–2006 (P = 0.0001); this was significant after accounting for differences in age and sex, particularly in non-Hispanic blacks. Prevalences of undiagnosed diabetes and pre-diabetes were generally stable, although the proportion of total diabetes that was undiagnosed decreased in Mexican Americans.CONCLUSIONS—Over 40% of people aged ≥20 years have hyperglycemic conditions, and prevalence is higher in minorities. Diagnosed diabetes has increased over time, but other conditions have been relatively stable.Diabetes and its complications remain major causes of morbidity and mortality in the U.S. (1). Estimated economic costs of diabetes in medical expenditures and lost productivity total $174 billion in the U.S. in 2007 (2). In 1999–2002, the crude prevalence of diabetes (diagnosed and undiagnosed) in the U.S. was 9.3%, of which 30% was undiagnosed based on fasting plasma glucose (FPG) (3). A further 26% had impaired fasting glucose (IFG). IFG increases the risk of diabetes (4), and both undiagnosed diabetes and IFG are associated with diabetes complications and risk factors (4,5). These prevalence data came from the National Health and Nutrition Examination Survey (NHANES), the only national survey that captures information on diabetes and pre-diabetes from an interview and FPG.In 2005–2006, an oral glucose tolerance test (OGTT) was added to NHANES, which had not been performed since NHANES 1988–1994. Whereas elevated FPG is determined more by impaired hepatic insulin resistance, elevated 2-h plasma glucose from an OGTT is determined predominantly by peripheral insulin resistance (4,6). The OGTT aids in detecting the total burden of diabetes and also impaired glucose tolerance (IGT). Two-hour plasma glucose values are more sensitive in the elderly (7), an increasing proportion of the U.S. population. IGT also predicts diabetes and is more commonly associated with cardiovascular disease risk factors and events than IFG (4,8).In this report, we analyze the prevalence of diagnosed diabetes, undiagnosed diabetes based on fasting and 2-h plasma glucose from an OGTT, and pre-diabetes (IFG or IGT) in people aged ≥12 years using data from NHANES 2005–2006. Results are presented by age, sex, and race/ethnicity. We compare these estimates with those from NHANES 1988–1994.The addition of the OGTT also allowed assessment of the agreement between diagnostic categories defined by fasting and 2-h plasma glucose. Although this was examined in NHANES 1988–1994 in those aged 40–74 years (9), a reexamination is appropriate given 1) the measurements in a wider age range in NHANES 2005–2006, 2) the change in criteria for IFG (lowered from 110 to 100 mg/dl) since that report (8), and 3) the rising prevalence of glucose abnormalities (3) and obesity (10).     

Trends in Diabetes Prevalence and Diabetes-Related Complications in Older Mexican Americans From 1993�C1994 to 2004�C2005

OBJECTIVE

Evidence has shown that Mexican Americans have a higher prevalence of diabetes and a greater risk for diabetes-related complications than non-Hispanic whites. However, no studies have described the changes in prevalence among older Mexican Americans. The purpose of this study was to expand on the current literature by examining the trends in diabetes prevalence and diabetes-related complications in Mexican Americans aged ≥75 years from 1993–1994 to 2004–2005.

RESEARCH DESIGN AND METHODS

The prevalences of self-reported diabetes and diabetes-related complications were estimated in the original cohort (1993–1994) and the new cohort (2004–2005) of the Hispanic Established Population for the Epidemiologic Study of the Elderly (Hispanic EPESE) and were compared across the two surveys.

RESULTS

The prevalence of diabetes among Mexican Americans aged ≥75 years has nearly doubled between 1993–1994 and 2004–2005 from 20.3 to 37.2%, respectively (P < 0.001). The increase in the prevalence of diabetes was similar across all sociodemographic factors. Diabetes complications did not change significantly between the two cohorts. However, the prevalence of having any lower-extremity function disability did increase between the two cohorts.

CONCLUSIONS

The prevalence of diabetes in older Mexican Americans has increased dramatically. At the same time, there has been no improvement in diabetes-related complications as has been found in the general older population. These findings heighten the urgency for more effective public health interventions targeted to this population. As diabetes and obesity become more prevalent in older adults, physicians should encourage appropriate management in older patients, including early detection and glycemic control.Diabetes is the seventh leading cause of death in the U.S., affecting 16.8 million Americans in 2006 (1). The prevalence of diabetes among individuals aged ≥75 years is projected to increase 336% by 2050 (2). This upward trend is attributed mainly to the aging of the population, an increase in obesity, and lifestyle changes (3–5). Simultaneously, there has been a decrease in the prevalence of several diabetes-related complications as a result of advancements in diabetes management (6).Older Hispanics are a rapidly growing segment of the U.S. population (7). During 1999 and 2002, diabetes was diagnosed in 24.9% of older Mexican Americans (aged ≥65 years) compared with only 14.3% of non-Hispanic white adults of the same age (8). Mexican Americans also have an increased risk and prevalence of diabetes-related complications and a higher disability rate compared with non-Hispanic whites (9,10). As overall life expectancy has increased, many Mexican Americans are living longer with more comorbidities including diabetes (9). Although several studies have examined the national trends of diabetes over the previous decades, no studies have examined the trends in diabetes prevalence and diabetes-related complications among older Mexican Americans. Hence, the purpose of this study was to expand on the current literature by examining the trends in diabetes prevalence and diabetes-related complications over the period 1993–1994 to 2004–2005, comparing two separate representative samples from the Hispanic Established Population for the Epidemiologic Study of the Elderly (Hispanic EPESE), a community-based study of older Mexican Americans (aged ≥65 years) residing in five southwestern states. This analysis builds on earlier work with the baseline data from this study, which showed high rates of diabetes and diabetes complications in older Mexican Americans in 1993–1994 (11–14).     

Prevalence of Diabetes and High Risk for Diabetes Using A1C Criteria in the U.S. Population in 1988�C2006

OBJECTIVE

We examined prevalences of previously diagnosed diabetes and undiagnosed diabetes and high risk for diabetes using recently suggested A1C criteria in the U.S. during 2003–2006. We compared these prevalences to those in earlier surveys and those using glucose criteria.

RESEARCH DESIGN AND METHODS

In 2003–2006, the National Health and Nutrition Examination Survey included a probability sample of 14,611 individuals aged ≥12 years. Participants were classified on glycemic status by interview for diagnosed diabetes and by A1C, fasting, and 2-h glucose challenge values measured in subsamples.

RESULTS

Using A1C criteria, the crude prevalence of total diabetes in adults aged ≥20 years was 9.6% (20.4 million), of which 19.0% was undiagnosed (7.8% diagnosed, 1.8% undiagnosed using A1C ≥6.5%). Another 3.5% of adults (7.4 million) were at high risk for diabetes (A1C 6.0 to <6.5%). Prevalences were disproportionately high in the elderly. Age-/sex-standardized prevalence was more than two times higher in non-Hispanic blacks and Mexican Americans versus non-Hispanic whites for diagnosed, undiagnosed, and total diabetes (P < 0.003); standardized prevalence at high risk for diabetes was more than two times higher in non-Hispanic blacks versus non-Hispanic whites and Mexican Americans (P < 0.00001). Since 1988–1994, diagnosed diabetes generally increased, while the percent of diabetes that was undiagnosed and the percent at high risk of diabetes generally decreased. Using A1C criteria, prevalences of undiagnosed diabetes and high risk of diabetes were one-third that and one-tenth that, respectively, using glucose criteria.

CONCLUSIONS

Although A1C detects much lower prevalences than glucose criteria, hyperglycemic conditions remain high in the U.S., and elderly and minority groups are disproportionately affected.The A1C test has recently been recommended for diagnosing diabetes, based on a detailed analysis of its attributes by an international expert committee (1). Laboratory-measured A1C is now as accurate and precise as glucose assays due to improvements in instrumentation and standardization. A1C samples can be obtained at any time, require no patient preparation, and are relatively stable at room temperature after collection. A1C has substantially less biologic variability and is unaffected by acute effects of stress or illness. As a measure of long-term glycemic exposure, A1C has been shown to be better and more consistently correlated with retinopathy in the setting of observational studies and clinical trials in type 1 and type 2 diabetic patients, which have established widely accepted A1C treatment goals for diabetes. A cut point of ≥6.5% for the diagnosis of diabetes was recommended by the committee as optimal for detecting a level of retinopathy thought to be diabetes specific and not due to other conditions (e.g., hypertension). A limitation of A1C for diagnosis is that the committee could not define a specific intermediate threshold at which increased risk for diabetes clearly begins. While there is a continuum of risk even at values into the normal range, the committee suggested the range of ≥6.0 to <6.5% to represent the highest risk for progression to diabetes and one at which preventive measures might be implemented, with additional consideration of prevention efforts at lower levels in the presence of other risk factors. The committee hoped that its report would serve as a stimulus to the scientific community and professional organizations for considering the A1C assay for diagnosis of diabetes.A change in diagnostic criteria has important public health implications pertaining to the magnitude of the population with diabetes or at high risk of diabetes. This report examines the prevalence of diagnosed and undiagnosed diabetes and high risk of diabetes based on self-report and A1C criteria in the U.S. population during 2003–2006. Prevalences are compared with those using the A1C criteria in 1988–1994 and 1999–2002. Finally, we compare the concordance in prevalence of undiagnosed diabetes using the new A1C criteria to criteria based on fasting plasma glucose and 2-h plasma glucose from an oral glucose tolerance test (OGTT).     

Secular Trends in Diabetes-Related Preventable Hospitalizations in the United States, 1998�C2006

OBJECTIVE

To examine secular trends in diabetes-related preventable hospitalizations among adults with diabetes in the U.S. from 1998 to 2006.

RESEARCH DESIGN AND METHODS

We used nationally representative data from the National Inpatient Sample to identify diabetes-related preventable hospitalizations. Based on the Agency for Healthcare Research and Quality''s Prevention Quality Indicators, we considered that hospitalizations associated with the following four conditions were preventable: uncontrolled diabetes, short-term complications, long-term complications, and lower-extremity amputations. Estimates of the number of adults with diabetes were obtained from the National Health Interview Survey. Rates of hospitalizations among adults with diabetes were derived and tested for trends.

RESULTS

Age-adjusted rates for overall diabetes-related preventable hospitalizations per 100 adults with diabetes declined 27%, from 5.2 to 3.8 during 1998–2006 (P_trend < 0.01). This rate decreased significantly for all but not for short-term complication (58% for uncontrolled diabetes, 37% for lower-extremity amputations, 23% for long-term complications [all P < 0.01], and 15% for the short-term complication [P = 0.18]). Stratified by age-group and condition, the decline was significant for all age-condition groups (all P < 0.05) except short-term complications (P = 0.33) and long-term complications (P = 0.08) for the age-group 18–44 years. The decrease was significant for all sex-condition combination subgroups (all P < 0.01).

CONCLUSIONS

We found a decrease in diabetes-related preventable hospitalizations in the U.S. from 1998 to 2006. This trend could reflect improvements in quality of primary care for individuals with diabetes.Hospitalizations related to diabetes are costly and account for a major portion of the total expenditure on diabetes. In 2007, hospitalizations in the U.S. attributable to diabetes cost $58 billion or 50% of the total direct medical expenditure for diabetes (1). Nevertheless, a large portion of hospitalizations for diabetes may be preventable if primary care is effectively delivered (2–4). Timely and effective diagnosis, treatment, and education can result in better management of diabetes, prevent the development or worsening of complications, and lead to lower hospitalization rates. Thus, diabetes is often referred to as an ambulatory care–sensitive condition, and its associated hospitalizations are often referred to as preventable hospitalizations. Examining the trends of preventable hospitalization would facilitate our understanding of how access to and quality of primary care for diabetes has or has not improved. However, few analyses of trends in preventable hospitalizations for individuals with diabetes have been published.The Agency for Healthcare Research and Quality (AHRQ) developed sets of disease and procedure codes using the ICD-9-CM to identify14 sets of preventable hospitalization conditions. Of the 14 conditions, four were for diabetes: uncontrolled diabetes, diabetes short-term complications, diabetes long-term complications, and lower-extremity amputations (5). The AHRQ also reported trends in rates of diabetes-related preventable hospitalizations from 1994 to 2000 (6). However, the rates reported by AHRQ used the total population (i.e., individuals with and without diabetes) as the denominator. Rates so calculated are sensitive to changes in diabetes prevalence and thus are not ideal for examining changes in access to and quality of ambulatory care for individuals with diabetes. Here, we used only adults with diabetes as the denominator to analyze national trends in the rates of diabetes-related preventable hospitalizations.     

Secular Changes in the Age-Specific Prevalence of Diabetes Among U.S. Adults: 1988–2010

OBJECTIVE

To examine the age-specific changes of prevalence of diabetes among U.S. adults during the past 2 decades.

RESEARCH DESIGN AND METHODS

This study included 22,586 adults sampled in three periods of the National Health and Nutrition Examination Survey (1988–1994, 1999–2004, and 2005–2010). Diabetes was defined as having self-reported diagnosed diabetes or having a fasting plasma glucose level ≥126 mg/dL or HbA_1c ≥6.5% (48 mmol/mol).

RESULTS

The number of adults with diabetes increased by 75% from 1988–1994 to 2005–2010. After adjusting for sex, race/ethnicity, and education level, the prevalence of diabetes increased over the two decades across all age-groups. Younger adults (20–34 years of age) had the lowest absolute increase in diabetes prevalence of 1.0%, followed by middle-aged adults (35–64) at 2.7% and older adults (≥65) at 10.0% (all P < 0.001). Comparing 2005–2010 with 1988–1994, the adjusted prevalence ratios (PRs) by age-group were 2.3, 1.3, and 1.5 for younger, middle-aged, and older adults, respectively (all P < 0.05). After additional adjustment for body mass index (BMI), waist-to-height ratio (WHtR), or waist circumference (WC), the adjusted PR remained statistically significant only for adults ≥65 years of age.

CONCLUSIONS

During the past two decades, the prevalence of diabetes increased across all age-groups, but adults ≥65 years of age experienced the largest increase in absolute change. Obesity, as measured by BMI, WHtR, or WC, was strongly associated with the increase in diabetes prevalence, especially in adults <65.Diabetes leads to microvascular complications and increased risk of cardiovascular disease morbidity and mortality. Unfortunately, the prevalence of diabetes in the U.S. has increased over the past 2 decades (1), paralleled by increasing obesity, aging, and a combination of changes in personal lifestyle, environmental conditions, population demographic characteristics, and improved survival of persons with diabetes (2,3). It is less clear whether the prevalence of diabetes (diagnosed and undiagnosed) has increased to the same degree across all age-groups and what role the presence of obesity plays in the prevalence of diabetes across age categories. Having a better understanding of the diabetes burden and changes over time across age categories of the U.S. population is essential for the delivery of primary and secondary prevention interventions, planning of health services, and allocation of limited health care resources.The U.S. National Health and Nutrition Examination Survey (NHANES) is an ongoing, national, multiple-phase, cross-sectional survey that contains information on self-reported diabetes status and laboratory measurements of blood glucose levels, thus allowing the examination of trends in both diagnosed and undiagnosed diabetes. In this study, we examined changes in the age-specific total diabetes prevalence among U.S. adults and the association of these changes with body mass index (BMI), waist-to-height ratio (WHtR), and waist circumference (WC) from 1988 to 2010 NHANES data.     

Racial Disparity of Eye Examinations Among the U.S. Working-Age Population With Diabetes: 2002–2009

OBJECTIVE

Diabetes care differs across racial and ethnic groups. This study aimed to assess the racial disparity of eye examinations among U.S. adults with diabetes.

RESEARCH DESIGN AND METHODS

Working-age adults (age 18–64 years) with diabetes were studied using data from the Medical Expenditure Panel Survey Household Component (2002–2009) including the Diabetes Care Survey. Racial and ethnic groups were classified as non-Hispanic whites and minorities. People reporting one or more dilated eye examination were considered to have received an eye examination in a particular year. Eye examination rates were compared between racial/ethnic groups for each year, and were weighted to national estimates. Multivariate adjusted odds ratios (aORs) and 95% CIs for racial/ethnic difference were assessed annually using logistic regression models. Other influencing factors associated with eye examination were also explored.

RESULTS

Whites had consistently higher unadjusted eye examination rates than minority populations across all 8 years. The unadjusted rates increased from 56% in 2002 to 59% in 2009 among whites, while the rates in minorities decreased from 56% in 2002 to 49% in 2009. The largest significant racial gap of 15% was observed in 2008, followed by 11%, 10%, and 7% in 2006, 2009, and 2005, respectively (P < 0.05). Minorities were less likely to receive eye examination (2006: aOR 0.75 [95% CI 0.57–0.99]; 2008: 0.61 [0.45–0.84]).

CONCLUSIONS

The racial/ethnic differences in eye examinations for patients with diabetes have persisted over the last decade. National programs to improve screening and monitoring of diabetic retinopathy are needed to target minority populations.     

Potential Mediators of Diabetes-Related Hearing Impairment in the U.S. Population: National Health and Nutrition Examination Survey 1999�C2004

OBJECTIVE

We examined potential mediators of the reported association between diabetes and hearing impairment.

RESEARCH DESIGN AND METHODS

Data come from 1,508 participants, aged 40–69 years, who completed audiometric testing during 1999–2004 in the National Health and Nutrition Examination Survey (NHANES). We defined hearing impairment as the pure-tone average >25 decibels hearing level of pure-tone thresholds at low/mid (500, 1,000, and 2,000 Hz) and high (3,000, 4,000, 6,000, and 8,000 Hz) frequencies. Using logistic regression, we examined whether controlling for vascular or neuropathic conditions, cardiovascular risk factors, glycemia, or inflammation diminished the association between diabetes and hearing impairment.

RESULTS

Diabetes was associated with a 100% increased odds of low/mid-frequency hearing impairment (odds ratio 2.03 [95% CI 1.32–3.10]) and a 67% increased odds of high-frequency hearing impairment (1.67 [1.14–2.44]) in preliminary models after controlling for age, sex, race/ethnicity, education, smoking, and occupational noise exposure. Adjusting for peripheral neuropathy attenuated the association with low/mid-frequency hearing impairment (1.70 [1.02–2.82]). Adjusting for albuminuria and C-reactive protein attenuated the association with high-frequency hearing impairment (1.54 [1.02–2.32] and 1.50 [1.01–2.23], respectively). Diabetes was not associated with high-frequency hearing impairment after controlling for A1C (1.09 [0.60–1.99]) but remained associated with low/mid-frequency impairment. We found no evidence suggesting that our observed relationship between diabetes and hearing impairment is due to hypertension or dyslipidemia.

CONCLUSIONS

Mechanisms related to neuropathic or microvascular factors, inflammation, or hyperglycemia may be mediating the association of diabetes and hearing impairment.Diabetes is associated with hearing impairment in population-based studies (1,2). Diabetes-related hearing impairment has been described as sensorineural in origin, implying that the lesion may be cochlear or of the eighth cranial nerve, but evidence favoring a specific mechanism is insufficient and contradictory (3). One possibility is that microvascular changes, which often lead to nephropathy and retinopathy, also affect the cochlear vasculature. Thickened basilar membranes and capillaries of the stria vascularis and atherosclerotic narrowing of the internal auditory artery were found among autopsied people who had diabetes but not in people without diabetes (4,5). Diabetes is also associated with neuropathic and peripheral artery complications that contribute to diabetic foot ulcers (6). Atrophy of the spiral ganglion and demyelination of the eighth cranial nerve among autopsied diabetic patients suggest a neurological etiology to diabetes-related hearing impairment (5). Regardless of whether the primary lesion is angiopathic or neuropathic, hyperglycemia may contribute (7).Cardiovascular disease, hypertension, and other cardiovascular risk factors are associated with hearing impairment (8–10). Because people with diabetes have a greater risk of these conditions than those without diabetes (11,12), the relationship between diabetes and hearing impairment may be attributable to a greater prevalence or severity of cardiovascular factors.Establishing effective interventions to disrupt the pathogenesis of diabetes-related hearing impairment will depend on understanding the mechanisms. This investigation studies potential mediators of the relationship between diabetes and hearing impairment. Specifically, we examine whether the presence of vascular or neuropathic conditions, cardiovascular risk factors, glycemia, or a marker of inflammation explain the association between diabetes and hearing impairment.     

Incident Dysglycemia and Progression to Type 1 Diabetes Among Participants in the Diabetes Prevention Trial�CType 1

OBJECTIVE

We studied the incidence of dysglycemia and its prediction of the development of type 1 diabetes in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether dysglycemia was sustained.

RESEARCH DESIGN AND METHODS

Participants (n = 515) in the Diabetes Prevention Trial–Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident dysglycemia at the 6-month visit was assessed for type 1 diabetes prediction.

RESULTS

Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of dysglycemia over a maximum follow-up of 7 years. Dysglycemia at the 6-month visit was highly predictive of the development of type 1 diabetes, both in those aged <13 years (P < 0.001) and those aged ≥13 years (P < 0.01). Those aged <13 years with dysglycemia at the 6-month visit had a high cumulative incidence (94% estimate by 5 years). Among those who developed type 1 diabetes after a dysglycemic OGTT and who had at least two OGTTs after the dysglycemic OGTT, 33 of 64 (52%) reverted back to a normal OGTT. However, 26 (79%) of the 33 then had another dysglycemic OGTT before diagnosis.

CONCLUSIONS

ICA-positive individuals with normal glucose tolerance had a high incidence of dysglycemia. Incident dysglycemia in those who are ICA positive is strongly predictive of type 1 diabetes. Children with incident dysglycemia have an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon before the onset of type 1 diabetes.There is increasing evidence that impaired glucose tolerance (IGT) is a predictor and common precursor of type 1 diabetes (1–3). Still, little is known about the incidence of IGT and other forms of dysglycemia in individuals who have pancreatic autoantibodies and normal glucose tolerance. In addition, there is no information about the risk of type 1 diabetes when dysglycemia occurs in those individuals. Moreover, it is not known whether dysglycemia is sustained once it occurs.We used data from the Diabetes Prevention Trial–Type 1 (DPT-1) (4,5) to examine these questions. In addition to IGT, impaired fasting glucose (IFG) and high glucose values at intermediate times (between fasting and 2 h) during oral glucose tolerance tests (OGTTs), termed indeterminate glycemia (INDET), were included as other forms of dysglycemia in the analyses. Glucose levels at intermediate times have been shown to be predictive of type 1 diabetes (6,7).Information regarding the incidence of these various forms of dysglycemia and their prediction of type 1 diabetes should be helpful for understanding the pathogenesis and natural history of type 1 diabetes. Such information should also be useful for improving type 1 diabetes prevention trials.     

Fewer Major Amputations Among Individuals With Diabetes in Finland in 1997�C2007: A population-based study

OBJECTIVE

Complications occur in diabetes despite rigorous efforts to control risk factors. Since 2000, the National Development Programme for the Prevention and Care of Diabetes has worked to halve the incidence of amputations in 10 years. Here we evaluate the impact of the efforts undertaken by analyzing the major amputations done in 1997–2007.

RESEARCH DESIGN AND METHODS

All individuals with diabetes (n = 396,317) were identified from comprehensive national databases. Data on the first major amputations (n = 9,481) performed for diabetic and nondiabetic individuals were obtained from the National Hospital Discharge Register.

RESULTS

The relative risk for the first major amputation was 7.4 (95% CI 7.2–7.7) among the diabetic versus the nondiabetic population. The standardized incidence of the first major amputation decreased among the diabetic and nondiabetic populations (48.8 and 25.2% relative risk reduction, respectively) over 11 years, and the time from the registration of diabetes to the first major amputation was significantly longer, on average 1.2 years more. The cumulative five-year postamputation mortality among diabetic individuals was 78.7%.

CONCLUSIONS

In our nationwide diabetes database, the duration from the registration of diabetes to the first major amputation increased, and the incidence of major amputations decreased almost 50% in 11 years. Approximately half of this change was due to the increasing size of the diabetic population. The risk for major amputation is more than sevenfold that among the nondiabetic population. These results pose a continuous challenge to improve diabetes care.Diabetes is increasing rapidly in Finland (1). For this reason, the National Development Programme for the Prevention and Care of Diabetes (DEHKO) was established for the years 2000–2010 (2). The program has specific goals that aim to reduce the complications of diabetes; one of them is to halve the incidence of lower limb amputations.The majority of amputations are performed for diabetic individuals. In Germany, 66% of lower limb amputations were performed for patients with diabetes; the relative risk was 8.8 for men and 5.7 for women compared with that for the nondiabetic population (3). The incidence of lower limb amputations among diabetic populations has varied from 2.1 to 13.7 per 1,000 person-years (4). In Suffolk, U.K., the incidence of major amputations was as low as 1.62 (5), and, in Sweden, the incidence of the first above-transmetatarsal-level amputation was 1.92 for women and 1.97 for men with diabetes (6). The amputation risk was eightfold (6).Falling amputation trends are described. Among type 1 diabetic patients in Sweden, the relative risk of lower limb amputation was 0.6 during the most recent 5-year period compared against the 5-year period before the year 2000 (7). In Scotland, the incidence of major amputations decreased from 5.1 to 2.9 per 1,000 patients with diabetes in 7 years (8). In Suffolk, U.K., major amputations decreased 82% from 1995 to 2005 (9).A great deal of the improvement in amputation trends is attributed to diabetes control programs. In the U.K., a control program led to a drop in the amputation incidence from 5.6 to 1.76 (10). In South Carolina, an education program brought about a decrease in lower limb amputations that was faster than that in other parts of the U.S. (11). Vascular surgery has an impact: in Denmark, a sevenfold increase in vascular surgical activity was associated with a 75% decrease in major amputations from 1981 to 1995 (12).It is still unclear whether the impact of programs is related to earlier diagnosis of diabetes or reflects a true effect of improved care. Multidisciplinary teamwork focusing on foot care and a continuous prospective audit has been shown to be beneficial (9). A thorough analysis of comprehensive register data may widen the perspective given by figures on amputation incidence among the diabetic population.The aim of our study was to analyze the first major amputations among diabetic individuals identified from comprehensive national databases during 1997–2007 and to evaluate the impact of efforts to improve diabetes care in Finland. Trends in amputation rates, time from the registration of diabetes to the first major amputation, and mortality were compared by sex and age-groups within and between diabetic and nondiabetic populations.     

Cystatin C– and Creatinine-Based Estimated Glomerular Filtration Rate,Vascular Disease,and Mortality in Persons With Diabetes in the U.S.

OBJECTIVE

Serum cystatin C is an alternative to serum creatinine for estimating glomerular filtration rate (GFR), since cystatin C is less influenced by age and muscle mass. Among persons with diabetes, we compared the performance of GFR estimated using cystatin C (eGFR_cys) with that using creatinine (eGFR_cr) for the identification of reduced kidney function and its association with diabetes complications.

RESEARCH DESIGN AND METHODS

We analyzed data from adult participants from the 1999–2002 National Health and Nutrition Examination Survey with available cystatin C (N = 4,457). Kidney function was dichotomized as preserved (eGFR ≥60 mL/min/1.73 m²) or reduced (eGFR <60 mL/min/1.73 m²) using the 2012 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C and the 2009 CKD-EPI creatinine equations.

RESULTS

Among 778 persons with diabetes, the prevalence of reduced kidney function was 16.5% using eGFR_cr and 22.0% using eGFR_cys. More persons with diabetes were reclassified from preserved kidney function by eGFR_cr to reduced kidney function by eGFR_cys than persons without diabetes (odds ratio 3.1 [95% CI 1.9–4.9], P < 0.001). The associations between lower eGFR and higher prevalence of albuminuria, retinopathy, peripheral arterial disease, and coronary artery disease were robust regardless of filtration marker. Similarly, the risk of all-cause mortality increased with lower eGFR_cr and eGFR_cys. Only lower eGFR_cys was significantly associated with cardiovascular mortality.

CONCLUSIONS

More persons with diabetes had reduced kidney function by eGFR_cys than by eGFR_cr, and lower eGFR_cys was strongly associated with diabetes complications. Whether eGFR_cys is superior to eGFR_cr in approximating true kidney function in a diabetic population requires additional study.     

Trends in types of calls managed by U.S. poison centers 2000–2015

Aim: The number of cases reported to poison centers has decreased since 2008 but there is evidence that the complexity of calls is increasing.

Objectives: The objectives are to evaluate national poison center data for trends in reason and how these changes effect management site, medical outcomes, and poison center workload.

Methods: Data regarding reason, age, management site, and medical outcome were extracted from annual reports of the National Poison Data System from 2000 to 2015. The proportion of cases by year were determined for unintentional and intentional exposures. Analysis of data from a single poison center from 2005 to 2015 compared the number of interactions between poison center staff and callers for unintentional versus intentional reasons.

Results: Trend analyses found that from 2000 to 2015 the percent of unintentional cases decreased (from 85.9 to 78.4%, p?p?p?Discussion: Poison centers are managing more intentional exposures and fewer unintentional exposures. Intentional exposures require more poison center staff expertise and time.

Conclusion: Looking only at poison center total call volume may not be an adequate method to gauge productivity.     

Life Years Lost and Lifetime Health Care Expenditures Associated With Diabetes in the U.S., National Health Interview Survey, 1997–2000

OBJECTIVEThis study analyzed the lifetime health care expenditures and life years lost associated with diabetes in the U.S.RESULTSPredicted life expectancy for patients with diabetes and without diabetes demonstrated an inverted U shape across most BMI classifications, with highest life expectancy being for the overweight. Lifetime health care expenditures were higher for whites than blacks and for females than males. Using U.S. adults aged 50 years as an example, we found that diabetic white females with a BMI >40 kg/m² had 17.9 remaining life years and lifetime health expenditures of $185,609, whereas diabetic white females with normal weight had 22.2 remaining life years and lifetime health expenditures of $183,704.CONCLUSIONSOur results show that diabetes is associated with large decreases in life expectancy and large increases in lifetime health care expenditures. In addition to decreasing life expectancy by 3.3 to 18.7 years, diabetes increased lifetime health care expenditures by $8,946 to $159,380 depending on age-race-sex-BMI classification groups.     

Associations of Serum Concentrations of 25-Hydroxyvitamin D and Parathyroid Hormone With Surrogate Markers of Insulin Resistance Among U.S. Adults Without Physician-Diagnosed Diabetes: NHANES, 2003�C2006

OBJECTIVE

To examine whether concentrations of serum 25-hydroxyvitamin D (25[OH]D) and parathyroid hormone (PTH) are associated with surrogate markers of insulin resistance (IR) in U.S. adults without physician-diagnosed diabetes.

RESEARCH DESIGN AND METHODS

Cross-sectional data (n = 3,206) from the National Health and Nutrition Examination Survey (NHANES) 2003–2006 were analyzed.

RESULTS

The age-adjusted prevalence of hyperinsulinemia, high homeostasis model assessment-IR, high GHb, and fasting and 2-h hyperglycemia decreased linearly across quintiles of 25(OH)D but increased linearly across quintiles of PTH (except for a quadratic trend for fasting hyperglycemia). After extensive adjustment for potential confounders, the relationships between 25(OH)D and the markers of IR and 2-h hyperglycemia persisted. Only hyperinsulinemia was positively associated with PTH (P < 0.05).

CONCLUSIONS

Among U.S. adults without physician-diagnosed diabetes, low concentrations of serum 25(OH)D were associated with markers of IR. The role of PTH in IR deserves further investigation.The role of vitamin D and parathyroid hormone (PTH) in metabolic syndrome and diabetes is receiving increased attention. Insulin resistance (IR) may represent a potential mechanism linking vitamin D and PTH to these conditions. The inverse associations between vitamin D and fasting insulin concentrations or the homeostasis model assessment of IR (HOMA-IR) index have been reported in some (1–5) but not all studies (6). Moreover, evidence linking PTH to markers of IR is limited and inconsistent (7–9). This study examined whether serum 25-hydroxyvitamin D (25[OH]D) and PTH are associated with surrogate markers of IR in U.S. adults without physician-diagnosed diabetes.     

Association Between Iron Deficiency and A1C Levels Among Adults Without Diabetes in the National Health and Nutrition Examination Survey, 1999�C2006

OBJECTIVE

Iron deficiency has been reported to elevate A1C levels apart from glycemia. We examined the influence of iron deficiency on A1C distribution among adults without diabetes.

RESEARCH DESIGN AND METHODS

Participants included adults without self-reported diabetes or chronic kidney disease in the National Health and Nutrition Examination Survey 1999–2006 who were aged ≥18 years of age and had complete blood counts, iron studies, and A1C levels. Iron deficiency was defined as at least two abnormalities including free erythrocyte protoporphyrin >70 μg/dl erythrocytes, transferrin saturation <16%, or serum ferritin ≤15 μg/l. Anemia was defined as hemoglobin <13.5 g/dl in men and <12.0 g/dl in women.

RESULTS

Among women (n = 6,666), 13.7% had iron deficiency and 4.0% had iron deficiency anemia. Whereas 316 women with iron deficiency had A1C ≥5.5%, only 32 women with iron deficiency had A1C ≥6.5%. Among men (n = 3,869), only 13 had iron deficiency and A1C ≥5.5%, and only 1 had iron deficiency and A1C ≥6.5%. Among women, iron deficiency was associated with a greater odds of A1C ≥5.5% (odds ratio 1.39 [95% CI 1.11–1.73]) after adjustment for age, race/ethnicity, and waist circumference but not with a greater odds of A1C ≥6.5% (0.79 [0.33–1.85]).

CONCLUSIONS

Iron deficiency is common among women and is associated with shifts in A1C distribution from <5.5 to ≥5.5%. Further research is needed to examine whether iron deficiency is associated with shifts at higher A1C levels.A1C is formed by the glycation of the terminal valine of the β-chain of hemoglobin. It is used commonly as a screening test for diabetes in clinical practice (1). A1C may be less susceptible than other measures of glycemia to temporary fluctuations caused by diet, physical activity, or illness as well as differences in local testing standards; as a result, an expert committee has recently endorsed an A1C ≥6.5% as diagnostic for diabetes (1).Previous studies have reported that depletion of iron stores may alter the glycation rate of hemoglobin and elevate A1C concentrations, independent of glycemia (2). Iron deficiency may be present without associated anemia (3). Although iron deficiency is the most common nutritional deficiency (3), the clinical relevance of iron deficiency on the use of A1C as a screening test for diabetes has not been studied. Reproductive-age women are particularly vulnerable to iron deficiency, reflecting iron loss through menstruation and pregnancy. In the Third National Health and Nutrition Examination Survey (NHANES) 1988–1994 and later NHANES waves, >11% of women had iron deficiency (3,4).Using a recent population-based sample of U.S. adults, we examined the distribution of A1C by iron deficiency status among adults without known diabetes. We hypothesized that adults with iron deficiency would be more likely to have elevated A1C levels, even after consideration of fasting plasma glucose. We also hypothesized that any differences would persist after adjustment for other factors associated with A1C and iron deficiency, including age, race/ethnicity, and waist circumference.     

Cystic Fibrosis�CRelated Diabetes: Current Trends in Prevalence, Incidence, and Mortality

OBJECTIVE

Cystic fibrosis (CF)-related diabetes (CFRD) diagnosis and management have considerably changed since diabetes was first shown to be associated with a poor prognosis in subjects with CF. Current trends in CFRD prevalence, incidence, and mortality were determined from a comprehensive clinical database.

RESEARCH DESIGN AND METHODS

Data were reviewed from 872 CF patients followed at the University of Minnesota during three consecutive intervals: 1992–1997, 1998–2002, and 2003–2008.

RESULTS

CFRD is currently present in 2% of children, 19% of adolescents, and 40–50% of adults. Incidence and prevalence are higher in female subjects aged 30–39 years; otherwise, there are no sex differences. In younger individuals, CFRD without fasting hyperglycemia predominates, but fasting hyperglycemia prevalence rises with age. CFRD mortality has significantly decreased over time. From 1992–1997 to 2003–2008, mortality rate in female subjects dropped by >50% from 6.9 to 3.2 deaths per 100 patient-years and in male subjects from 6.5 to 3.8 deaths per 100 patient-years. There is no longer a sex difference in mortality. Diabetes was previously diagnosed as a perimorbid event in nearly 20% of patients, but of 61 patients diagnosed with diabetes during 2003–2008, only 2 died. Lung function but not nutritional status is still worse in CF patients with diabetes compared with those without diabetes. Nutritional status and pulmonary status are similar between patients without fasting hyperglycemia and those with fasting hyperglycemia.

CONCLUSIONS

Previously noted sex differences in mortality have disappeared, and the gap in mortality between CF patients with and without diabetes has considerably narrowed. We believe that early diagnosis and aggressive treatment have played a major role in improving survival in these patients.Diabetes is the most common comorbidity in subjects with cystic fibrosis (CF). Of particular concern is the fact that the additional diagnosis of diabetes has been associated with significantly greater mortality, especially in women. In 1988, we reported that compared with >60% of the nondiabetic CF population, <25% of individuals with diabetes survived until age 30 years (1). We subsequently published data examining mortality at the University of Minnesota Cystic Fibrosis Center during the 15-year period between 1987 and 2002 and reached the startling conclusion that diabetes reduced survival in women by >16 years (2). Unlike the general population, patients with CF-related diabetes (CFRD) are not at risk for atherosclerotic cardiovascular disease (3); as in other individuals with CF, death occurs from chronic inflammatory lung disease. In several studies, pulmonary function and nutritional status have been shown to be intimately linked and to be worse in patients with CFRD compared with CF patients without diabetes (4–8). It has been postulated that this is a consequence of the protein catabolic effects of insulin deficiency combined with the proinflammatory effects of hyperglycemia.Since 1987, experimental studies and careful clinical data collection have progressively increased our understanding of CFRD, and it is managed much differently today than even 5 years ago. With routine annual oral glucose tolerance test (OGTT) outpatient screening and careful inpatient glucose monitoring, patients are not likely to experience long periods of undiagnosed diabetes. We are much better able to accurately report prevalence and incidence of CFRD, particularly in the older age-groups, because CF patients are living longer. Early institution of intensive basal-bolus insulin therapy has become routine in the last 5 years. Thus, patients are diagnosed earlier and treated more aggressively than ever before. The current database review was undertaken to determine whether modern diabetes screening and management have influenced prevalence, incidence, and mortality figures.