Dietary Patterns and Risk for Diabetes: The Multiethnic Cohort

OBJECTIVE

The high diabetes incidence among Japanese Americans and Native Hawaiians cannot be explained by BMI. Therefore, we examined the influence of three dietary patterns of “fat and meat,” “vegetables,” and “fruit and milk” on diabetes risk in the Hawaii component of the Multiethnic Cohort with 29,759 Caucasians, 35,244 Japanese Americans, and 10,509 Native Hawaiians.

RESEARCH DESIGN AND METHODS

Subjects aged 45–75 years completed a baseline food frequency questionnaire. After 14 years of follow-up, 8,587 subjects with incident diabetes were identified through self-reports or health plan linkages. Risk was assessed using Cox regression stratified by age and adjusted for ethnicity, BMI, physical activity, education, total energy, smoking, alcohol intake, marital status, and hypertension.

RESULTS

Fat and meat was significantly associated with diabetes risk in men (hazard ratio 1.40 [95% CI 1.23–1.60], P_trend < 0.0001) and women (1.22 [1.06–1.40], P_trend = 0.004) when extreme quintiles were compared. Except in Hawaiian women, the magnitude of the risk was similar across ethnic groups although not always significant. After stratification by BMI, fat and meat remained a predictor of disease primarily among overweight men and among overweight Japanese women. Vegetables lowered diabetes risk in men (0.86 [0.77–0.95], P_trend = 0.004) but not in women, whereas fruit and milk seemed to be more beneficial in women (0.85 [0.76–0.96], P_trend = 0.005) than in men (0.92 [0.83–1.02], P_trend = 0.04).

CONCLUSIONS

Foods high in meat and fat appear to confer a higher diabetes risk in all ethnic groups, whereas the effects of other dietary patterns vary by sex and ethnicity.Native Hawaiians have extremely high rates of obesity and diabetes, but despite their relatively low body weight, individuals with Japanese ancestry are also disproportionately affected by diabetes (1). Among the >44,000 Japanese Americans, 14,000 Native Hawaiians, and 35,000 Caucasians in the Hawaii component of the Multiethnic Cohort (MEC), a previous analysis had found diabetes incidence rates of 15.5, 12.5, and 5.8 per 1,000 person-years, respectively, that could not be explained by BMI (2). Dietary patterns have been identified as additional predictors of disease but have only rarely been investigated prospectively among non-Caucasian populations (3–5). The most commonly identified patterns are the so-called “western,” “unhealthy,” or “conservative” pattern (3–11), which is high in meat, high-fat foods, and sweets, and the “prudent” or “healthy” pattern, rich in fruit and vegetables (3–8,10,12,13). With the goal to contribute to the prevention of diabetes, we examined the effect of three dietary patterns, “fat and meat,” “vegetables,” and “fruit and milk,” which had been previously identified in the MEC, on diabetes risk (14).     

Pancreatic Islet Autoantibodies as Predictors of Type 1 Diabetes in the Diabetes Prevention Trial�CType 1

OBJECTIVE

There is limited information from large-scale prospective studies regarding the prediction of type 1 diabetes by specific types of pancreatic islet autoantibodies, either alone or in combination. Thus, we studied the extent to which specific autoantibodies are predictive of type 1 diabetes.

RESEARCH DESIGN AND METHODS

Two cohorts were derived from the first screening for islet cell autoantibodies (ICAs) in the Diabetes Prevention Trial–Type 1 (DPT-1). Autoantibodies to GAD 65 (GAD65), insulinoma-associated antigen-2 (ICA512), and insulin (micro-IAA [mIAA]) were also measured. Participants were followed for the occurrence of type 1 diabetes. One cohort (Questionnaire) included those who did not enter the DPT-1 trials, but responded to questionnaires (n = 28,507, 2.4% ICA⁺). The other cohort (Trials) included DPT-1 participants (n = 528, 83.3% ICA⁺).

RESULTS

In both cohorts autoantibody number was highly predictive of type 1 diabetes (P < 0.001). The Questionnaire cohort was used to assess prediction according to the type of autoantibody. As single autoantibodies, ICA (3.9%), GAD65 (4.4%), and ICA512 (4.6%) were similarly predictive of type 1 diabetes in proportional hazards models (P < 0.001 for all). However, no subjects with mIAA as single autoantibodies developed type 1 diabetes. As second autoantibodies, all except mIAA added significantly (P < 0.001) to the prediction of type 1 diabetes. Within the positive range, GAD65 and ICA autoantibody titers were predictive of type 1 diabetes.

CONCLUSIONS

The data indicate that the number of autoantibodies is predictive of type 1 diabetes. However, mIAA is less predictive of type 1 diabetes than other autoantibodies. Autoantibody number, type of autoantibody, and autoantibody titer must be carefully considered in planning prevention trials for type 1 diabetes.Autoantibodies to islet cell antigens are known predictors of type 1 diabetes and are commonly present at its diagnosis (1–12). Islet cell autoantibodies (ICAs), the first identified (1,2), actually represent autoimmunity to several different antigens. More recently, autoantibodies specific to single tissue antigens, termed biochemical autoantibodies, have been identified (4,7,8,11–13). These include antibodies to GAD 65 (GAD65), the antibody to an insulinoma-associated antigen-2 (ICA512), and antibodies to insulin (IAA).Type 1 diabetes prevention trials have used autoantibodies to screen for individuals at increased risk who might be candidates for participation (14–16). The Diabetes Prevention Trial–Type 1 (DPT-1) assessed parenteral and oral insulin as potential prevention modalities. First- and second-degree relatives of type 1 diabetic patients were screened for the presence of ICA, which was required for eligibility. Although not relevant to the trials, biochemical autoantibodies were subsequently measured from screening samples to learn more about their prediction of type 1 diabetes. The prevalence of autoantibodies according to various subgroups has been reported for DPT-1 (17).We used two DPT-1 cohorts to examine the prediction of type 1 diabetes by ICA and biochemical autoantibodies, as few large-scale studies have examined the prediction of type 1 diabetes by a variety of single autoantibodies in large numbers of individuals of whom many ultimately developed type 1 diabetes. One cohort includes DPT-1 participants who participated in the trials (the Trials cohort), and the other cohort includes participants who did not participate in either trial but responded to questionnaires (the Questionnaire cohort) used to ascertain information regarding the diagnosis of type 1 diabetes. The differing perspectives of these two cohorts and the large number of individuals studied, almost 30,000, provide a unique opportunity for studying the prediction of type 1 diabetes by autoantibodies.     

Rising rates of all types of diabetes in south Asian and non-south Asian children and young people aged 0-29 years in West Yorkshire, U.K., 1991-2006

OBJECTIVE

To investigate incidence trends of all diabetes types in all children and young people and in the south Asian subpopulation.

RESEARCH DESIGN AND METHODS

Annual incidence per 100,000 and time trends (1991–2006) were analyzed for 2,889 individuals aged 0–29 years diagnosed with diabetes while resident in West Yorkshire, U.K.

RESULTS

Diagnoses comprised type 1 (83%), type 2 (12%), maturity-onset diabetes of the young (0.7%), “J”-type/other (0.1%), and uncertain/unclassified (4%). There was a lower incidence of type 1 and a threefold excess of type 2 in south Asians compared with non-south Asians. Type 1 incidence leveled out and type 2 increased after the first south Asian case of type 2 was diagnosed in 1999. Type 2 and unclassified diabetes incidence rose in all population subgroups.

CONCLUSIONS

The burden of diabetes increased over time for both ethnic groups, with a significant excess of type 2 diabetes in south Asians. The rising incidence of type 1 diabetes in south Asians attenuated as type 2 diabetes increased after 1999.Type 1 diabetes incidence is stable in young adults (1,2), contrasting with rising rates in children (3,4). In south Asia, the incidence is low (4), but south Asian children had rates similar to the indigenous population in the U.K. up to 1999 (5). An increasing incidence of type 2 diabetes in children and young people is reported in the U.K. and worldwide (6–8), but in Asia it has emerged more quickly—and in younger age groups—than elsewhere (9). In this report we have analyzed incidence trends in all types of diabetes to assess the total burden of diabetes in children and young people.     

Associations between media consumption habits, physical activity, socioeconomic status, and glycemic control in children, adolescents, and young adults with type 1 diabetes

OBJECTIVE

To evaluate the relationship between media consumption habits, physical activity, socioeconomic status, and glycemic control in youths with type 1 diabetes.

RESEARCH DESIGN AND METHODS

In the cross-sectional study, self-report questionnaires were used to assess media consumption habits, physical activity, and socioeconomic status in 296 children, adolescents, and young adults with type 1 diabetes. Clinical data and HbA_1c levels were collected. Risk factors were analyzed by multiple regression.

RESULTS

Youths with type 1 diabetes (aged 13.7 ± 4.1 years, HbA_1c 8.7 ± 1.6%, diabetes duration 6.1 ± 3.3 years) spent 2.9 ± 1.8 h per day watching television and using computers. Weekly physical activity was 5.1 ± 4.5 h. Multiple regression analysis identified diabetes duration, socioeconomic status, and daily media consumption time as significant risk factors for glycemic control.

CONCLUSIONS

Diabetes duration, socioeconomic status, and daily media consumption time, but not physical activity, were significant risk factors for glycemic control in youths with type 1 diabetes.The pivotal Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) study demonstrate that poor glycemic control is associated with an increased risk of developing complications in type 1 diabetes (1). Various factors contributing to glycemic control have been identified (2). Immutable parameters such as age, sex, diabetes duration, and socioeconomic status have a major effect on metabolic control (2–6). Lower socioeconomic status is an important determinant for poor glycemic control (4,5). Modifiable factors influencing metabolic control are diabetes-related knowledge, frequency of blood glucose monitoring, and daily insulin dose (3,4,6,7). Lastly, psychosocial parameters are important in achieving good glycemic control (3–5,8–10). The influence of physical activity on metabolic control is unclear (9,11,12).Recent research addresses the influence of modern life habits on general health. Youths spend more and more time watching television and using computers. Many studies suggest that sedentary behaviors such as watching television lead to obesity in children (13,14). In one study in youths with type 1 diabetes, Margeirsdottir et al. (15) showed that poor metabolic control was associated with extensive television watching. However, the authors did not examine other covariables, such as socioeconomic status, which is associated with both glycemic control and media consumption (4,5,16,17). Hence, the aim of this study was to examine the impact of media consumption habits, physical activity, and socioeconomic status on glycemic control in youths with type 1 diabetes.     

Extended Family History of Diabetes and Autoimmune Diseases in Children With and Without Type 1 Diabetes

OBJECTIVE

To determine the extended family history of diabetes or autoimmune diseases in families with and without children having type 1 diabetes.

RESEARCH DESIGN AND METHODS

Three hundred case families and 381 control families were interviewed using structured questionnaires.

RESULTS

The proportion of case children having at least one relative with type 1 diabetes outside the nuclear family was higher than that of control children (50.3 vs. 31.8%, P < 0.001). The proportions of case and control children having relatives with type 2 diabetes or gestational diabetes were similar. Other autoimmune diseases occurred more frequently among the case children (9.7 vs. 1.1%, P < 0.001), in the case nuclear families (22.0 vs. 12.9%, P = 0.002) and in relatives outside the case nuclear family (72.0 vs. 62.2%, P = 0.007).

CONCLUSIONS

Type 1 diabetes and autoimmune diseases not only cluster in the nuclear families of children with type 1 diabetes but are also overrepresented in their extended families.First degree relatives of patients with type 1 diabetes clearly have an increased disease risk (1–5), but little information is available about the occurrence of type 1 diabetes outside the nuclear family (6). It is also unclear whether type 2 diabetes and gestational diabetes are more frequently present in the families of children with type 1 diabetes (7–9). Type 1 diabetes is known to be associated with other autoimmune diseases, but there is a scarcity of data on the frequency of autoimmune diseases among other family members (10).     

Physical Activity, Adiposity, and Diabetes Risk in Middle-Aged and Older Chinese Population: The Guangzhou Biobank Cohort Study

OBJECTIVE

Physical activity may modify the association of adiposity with type 2 diabetes. We investigated the independent and joint association of adiposity and physical activity with fasting plasma glucose, impaired fasting glucose, and type 2 diabetes in a Chinese population.

RESEARCH DESIGN AND METHODS

Middle-aged and older Chinese (n = 28,946, ≥50 years, 72.4%women) from the Guangzhou Biobank Cohort Study were examined in 2003–2008. Multivariable regression was used in a cross-sectional analysis.

RESULTS

BMI, waist circumference, and waist-to-hip ratio (WHR) were positively associated with type 2 diabetes after multiple adjustment, most strongly for WHR with odds ratio (OR) of 3.99 (95% CI 3.60–4.42) for highest compared with lowest tertile. Lack of moderate-to-vigorous physical activity, but not walking, was associated with diabetes with an OR of 1.29 (1.17–1.41). The association of moderate-to-vigorous activity with fasting glucose varied with WHR tertiles (P = 0.01 for interaction). Within the high WHR tertile, participants who had a lack of moderate-to-vigorous activity had an OR of 3.87 (3.22–4.65) for diabetes, whereas those who were active had an OR of 2.94 (2.41–3.59).

CONCLUSIONS

In this population, WHR was a better measure of adiposity-related diabetes risk than BMI or waist circumference. Higher moderate-to-vigorous activity was associated with lower diabetes risk, especially in abdominally obese individuals.Type 2 diabetes is a worldwide cause of morbidity and mortality. Adiposity, especially abdominal adiposity, seems to be at the core of development of hyperglycemia and type 2 diabetes (1). Increased physical activity may mitigate some of the diabetogenic impact of adiposity (2–4). Individuals who are obese but fit could even have a lower risk of mortality than those who are normal weight but unfit (5,6). However, being physically active does not completely abolish the obesity-related risk for cardiovascular disease and associated mortality (7). Adiposity is still the main risk factor for the development of type 2 diabetes (2–4,8). Although increased physical activity has been shown to be associated with reduced type 2 diabetes risk independent of adiposity, the protective effects may differ by the level of adiposity. However, the group that could benefit most from physical activity for the prevention of diabetes is still unclear (2–4,8–10).Understanding the relationship between adiposity and physical activity is important to stratify risk groups for the development of effective diabetes prevention strategies from public health and clinical perspectives. Most of the studies relate to Caucasians (2–4,8–10), whereas Asians, including Chinese and Indians, are possibly more vulnerable to insulin resistance (11). The number of Chinese adults with type 2 diabetes was estimated to be ∼28.1 million in 2000 and may double by 2030, with China being second only to India (12). The purpose of this study was to investigate the independent and joint association of adiposity and physical activity with fasting plasma glucose, impaired fasting glucose (IFG), and type 2 diabetes in 28,946 middle-aged and older Chinese participants in the Guangzhou Biobank Cohort Study.     

Pediatric Endocrinologists' Management of Children With Type 2 Diabetes

OBJECTIVE

To understand physician behaviors and attitudes in managing children with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A survey was mailed to a nationwide sample of pediatric endocrinologists (PEs).

RESULTS

A total of 40% of PEs surveyed responded (211 of 527). Concordance with current monitoring guidelines varied widely, ranging from 36% (foot care) to 93% (blood pressure monitoring). Given clinical vignettes addressing hyperlipidemia, hypertension, and microalbuminuria, only 34% of PEs were fully concordant with current treatment guidelines. Reported barriers included concerns about patient adherence, insufficient scientific evidence about treatment, and lack of familiarity with current recommendations. Providers aged ≤45 years or in clinical practice <10 years reported significantly more aggressive management behaviors and had higher concordance with guidelines.

CONCLUSIONS

Screening and management of pediatric type 2 diabetes varied widely among PEs, suggesting opportunities for quality improvement. More aggressive management of type 2 diabetes among younger providers may be related to recent training when type 2 diabetes was more common.The incidence of type 2 diabetes in children is increasing (1), and children with type 2 diabetes are at high risk to develop diabetes-related complications, including hyperlipidemia, hypertension, and microalbuminuria (2–4). Despite limited scientific evidence, several consensus statements on the assessment and management of pediatric type 2 diabetes have been developed (4–6). Current understanding of physician management of pediatric type 2 diabetes is limited (7–10). We conducted a survey to better understand pediatric endocrinologists'' (PEs'') behaviors and attitudes related to the management of pediatric type 2 diabetes.     

Does Blood Glucose Monitoring Increase Prior to Clinic Visits in Children With Type 1 Diabetes?

OBJECTIVE

To assess the occurrence of white coat adherence in families with children who have type 1 diabetes.

RESEARCH DESIGN AND METHODS

Blood glucose data were downloaded from meters of 72 children, aged 2–11 years, with type 1 diabetes at four consecutive clinic visits. Generalized estimating equations were used to analyze patterns of blood glucose monitoring (BGM) during the 28 days before each clinic visit.

RESULTS

More frequent BGM was associated with better glycemic control. Evidence of a white coat adherence effect, with BGM frequency increasing before a clinic visit, was found only among children with low A1C levels.

CONCLUSIONS

Highly motivated families who frequently monitor their child’s blood glucose increased the frequency of BGM before the child’s clinic visit. The additional monitoring may benefit the child by providing the physician with a wealth of blood glucose information to guide recommendations.Although more frequent blood glucose monitoring (BGM) has been associated with better glycemic control in children and adults with type 1 diabetes (1–3), to our knowledge, no studies have examined whether BGM frequency increases before a visit to the physician. There is a literature on “white coat adherence” (also referred to as white coat compliance and the “toothbrush effect”) (4,5)—a term used to connote an improvement in treatment adherence before the clinic appointment. Existing studies of white coat adherence have been conducted with adult epilepsy, HIV, and dermatology populations (6–8) and in pediatric epilepsy and dermatology populations (7,9). Adult patients increased their use of oral and topical medications for a short period before and after a clinic or physician appointment (10). This same pattern of white coat adherence was found in pediatric dermatology patients (7) but not in children with newly diagnosed epilepsy (9). However, no studies evaluating the occurrence of white coat adherence in pediatric patients with type 1 diabetes have been published to date. Therefore, the primary aim of this study was to use data downloaded from blood glucose meters at four consecutive clinic visits to determine if white coat adherence occurred in a sample of pediatric patients.White coat adherence could have significant implications for type 1 diabetes treatment recommendations. Patients might increase BGM before a clinic visit to please the physician by appearing highly adherent or to provide as much information as possible to guide treatment recommendations. In either case, increased BGM before a clinic visit does not represent the patient’s usual pattern of BGM and may mislead the physician into believing the patient’s BGM is more frequent than is actually the case.     

Age of islet autoantibody appearance and mean levels of insulin, but not GAD or IA-2 autoantibodies, predict age of diagnosis of type 1 diabetes: diabetes autoimmunity study in the young

OBJECTIVE

We evaluated predictors of progression to diabetes in children with high-risk HLA genotypes and persistent islet autoantibodies.

RESEARCH DESIGN AND METHODS

The Diabetes Autoimmunity Study in the Young (DAISY) followed 2,542 children with autoantibodies measured to GAD, IA-2, and insulin.

RESULTS

Persistent islet autoantibodies developed in 169 subjects, and 55 of those progressed to diabetes. Children expressing three autoantibodies showed a linear progression to diabetes with 74% cumulative incidence by the 10-year follow-up compared with 70% with two antibodies and 15% with one antibody (P < 0.0001). Both age of appearance of first autoantibody and insulin autoantibody (IAA) levels, but not GAD or IA-2 autoantibodies, were major determinants of the age of diabetes diagnosis (r = 0.79, P < 0.0001).

CONCLUSIONS

In the DAISY cohort, 89% of children who progressed to diabetes expressed two or more autoantibodies. Age of diagnosis of diabetes is strongly correlated with age of appearance of first autoantibody and IAA levels.Most of the trials to prevent type 1A diabetes target individuals in the preclinical phase of the disease, marked by the presence of persistent islet autoantibodies (1). Screening for autoantibodies to insulin (IAA) (2), GAD (3), and protein tyrosine IA-2 (ICA512) (4) is the mainstay of risk prediction (5). Factors correlating and potentially predictive of age of diagnosis of children followed from birth are less well characterized.     

Association of depressive symptoms with impaired glucose regulation, screen-detected, and previously known type 2 diabetes: findings from the Finnish D2D Survey

OBJECTIVE

To study the association between impaired glucose regulation (IGR), screen-detected type 2 diabetes, and previously known diabetes and depressive symptoms.

RESEARCH DESIGN AND METHODS

Altogether, 2,712 participants from three hospital districts in Finland attended a health examination. Cutoff scores ≥10 and ≥16 in the 21-item Beck Depression Inventory (BDI-21) were used for depressive symptoms. The participants were defined as having known diabetes if they reported diabetes. An oral glucose tolerance test was used to detect normal glucose regulation (NGR), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and screen-detected diabetes. The participants were defined as having IGR if they had IFG or IGT.

RESULTS

Prevalence of depressive symptoms, defined as a BDI-21 cutoff score ≥10, was 14.4% for those with NGR, 13.7% for those with IGR, 14.8% for those with screen-detected diabetes, and 26.4% for those with previously known diabetes. The corresponding prevalences for a cutoff score ≥16 were 3.4, 3.4, 4.2, and 7.5%, respectively. Compared with NGR and adjusted for demographic, lifestyle, and biological factors, the odds ratios for IGR, screen-detected diabetes, and previously known diabetes were 0.91 (95% CI 0.69–1.20), 0.70 (0.45–1.08), and 1.35 (0.84–2.15), respectively, for a cutoff score ≥10. For a cutoff score ≥16, the corresponding odds ratios were 1.05 (0.62–1.76), 0.87 (0.40–1.90), and 1.56 (0.69–3.50), respectively.

CONCLUSIONS

Participants with diagnosed diabetes had a higher prevalence of depressive symptoms than participants with NGR, IGR, and previously unknown diabetes. When potential confounding factors were included in the analysis, previously known diabetes was not significantly associated with depressive symptoms.It is widely recognized that depression is more common among people with diabetes than in the general population (1). However, previous studies (2–10) that have assessed the relationship between depressive symptoms and impaired glucose tolerance (IGT) or diabetes have been inconsistent. A German study (4) that included 4,597 subjects and a Dutch study (2) that included 4,747 participants found no association between type 2 diabetes and depressive symptoms. In a general-practice setting study that included 2,849 male and 3,160 female subjects, depression was not more prevalent in people with screen-detected diabetes or impaired glucose regulation (IGR) than in people with normal glucose regulation (NGR) (5). Contrary to these studies, within the Hertfordshire Cohort Study (6) there was a relationship between depression scores and diagnosed and previously undiagnosed diabetes. A U.S. study (8) including 4,293 U.S. veterans indicated that men with undiagnosed type 2 diabetes had nearly double the odds of major depression compared with those with normal fasting glucose.In 1992, it was stated about the relationship between depression and diabetes that “the etiology is unknown but is probably complex; and biological, genetic, and psychological factors remain as potential contributors. Several neuroendocrine and neurotransmitter abnormalities common to both depression and diabetes have been identified, adding to etiological speculations” (11). It has been suggested that stress-induced activation of the hypothalamic-pituitary-adrenal axis may result in the development of metabolic abnormalities and depression (12). In addition, possible neuroendocrine abnormalities associated with both diabetes and depressive symptoms may include abnormalities in vitamin B₁₂ and sex hormone–binding globulin (SHBG) levels. Low vitamin B₁₂ levels have been found to relate to type 2 diabetes (13) and depressive symptoms (14–16). Low levels of SHBG may predict diabetes (17). SHBG binds circulating sex hormones, which have been suggested to be associated with depressive symptoms (18). In addition to these biological factors, the observed association between diabetes and depressive symptoms could be a reflection of the burden of diabetes and comorbidities.In the present study, our aim was to analyze the prevalence of depressive symptoms in people with NGR, IGR (including impaired fasting glycemia and impaired glucose tolerance), screen-detected (previously unknown) diabetes, and previously known type 2 diabetes. Furthermore, our aim was to study the association between glucose tolerance and depressive symptoms, taking into account potential confounding demographic and biological factors as well as comorbidity.     

Fear of injury with physical activity is greater in adults with diabetes than in adults without diabetes

OBJECTIVE

Physical activity is a cornerstone of treatment for diabetes, yet people with diabetes perform less moderate and vigorous physical activity (MVPA) than people without diabetes. In contrast, whether differences in walking activity exist has been understudied. Diabetes-specific barriers to physical activity are one possible explanation for lower MVPA in diabetes. We hypothesized that people with diabetes would perform less walking and combined MVPA and would be less likely to anticipate increasing physical activity if barriers were theoretically absent, compared with people without diabetes.

RESEARCH DESIGN AND METHODS

We surveyed 1,848 randomly selected rural Colorado adult residents by telephone from 2002 to 2004. Respondents reported weekly walking and MVPA duration and their likelihood of increasing physical activity if each of seven barriers was theoretically absent.

RESULTS

People with diabetes (n = 129) had lower odds of walking and MVPA than people without diabetes (walking: adjusted odds ratio 0.62 [95% CI 0.40–0.95]; MVPA: adjusted odds ratio 0.60 [0.36–0.99]; ≥10 vs. <10 min/week, adjusted for age, sex, BMI, and ethnicity). Respondents with diabetes reported fear of injury as a barrier to physical activity more often than respondents without diabetes (56 vs. 39%; P = 0.0002), although this relationship was attenuated after adjusting for age and BMI (adjusted odds ratio 1.36 [0.93–1.99]).

CONCLUSIONS

Although walking is a preferred form of activity in diabetes, people with diabetes walk less than people without diabetes. Reducing fear of injury may potentially increase physical activity for people with diabetes, particularly in older and more overweight individuals.Physical activity is considered a cornerstone of diabetes treatment (1), yet people with diabetes are less physically active than people without diabetes, especially with regard to moderate and vigorous physical activity (MVPA) (2–4). Although MVPA optimally promotes cardiovascular health for people with diabetes, regular walking activity is associated with reduced cardiovascular mortality (5,6) and is the preferred activity of people with diabetes (3,7). To our knowledge, only two studies have compared walking activity by diabetes status using population-based samples (3,8). In summary, a handful of studies have demonstrated that diabetes is related to lower MVPA levels, but we need additional data to assess whether diabetes status is also related to lower walking activity levels.Identifying and removing barriers to physical activity is important because of the strong relationship between physical inactivity and cardiovascular disease in people with type 2 diabetes and the likely cardiovascular benefits for people with type 1 diabetes (5,6). Some barriers have been identified that may be considered diabetes specific, including “fear of hypoglycemia” (9,10), the presence of “bad feet due to diabetes” (11), and an “unwillingness to exercise in the presence of people who do not have type 2 diabetes” (12). In the laboratory setting, diabetes is associated with impaired submaximal exercise performance and greater perceived effort during low-intensity exercise (13). While these potential diabetes-specific barriers to physical activity have been identified, this area has been understudied.Other barriers to physical activity exist in people with type 2 diabetes, including lack of social support, lack of knowledge of the types of exercise to perform, health problems, pain/difficulty taking part in exercise, lack of local exercise facilities, and aversion to exercising in poor weather (12). Although several studies have identified barriers to physical activity in people with type 2 diabetes, only one study used population-based sampling (14), only one assessed whether usual activity levels influence barriers (12), and differences in barriers by diabetes status (diabetes vs. no diabetes) were not compared.The current study compares barriers to physical activity by diabetes status in a rural, biethnic population-based sample within two strata of physical activity: “less active” (<150 min weekly MVPA) and “more active” (≥150 min weekly MVPA). Because walking activity differences by diabetes status have been understudied, we also compared walking and MVPA differences in participants with and without diabetes. We hypothesized that people with diabetes would perform less walking and MVPA and would be less likely to anticipate increasing physical activity if barriers were theoretically absent, compared with people without diabetes.     

Postchallenge Glucose, A1C, and Fasting Glucose as Predictors of Type 2 Diabetes and Cardiovascular Disease: A 10-year prospective cohort study

OBJECTIVE

A1C has been proposed as a new indicator for high risk of type 2 diabetes. The long-term predictive power and comparability of elevated A1C with the currently used high-risk indicators remain unclear. We assessed A1C, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) as predictors of type 2 diabetes and cardiovascular disease (CVD) at 10 years.

RESEARCH DESIGN AND METHODS

This prospective population-based study of 593 inhabitants from northern Finland, born in 1935, was conducted between 1996 and 2008. An oral glucose tolerance test (OGTT) was conducted at baseline and follow-up, and A1C was determined at baseline. Those with a history of diabetes were excluded from the study. Elevated A1C was defined as 5.7–6.4%. Incident type 2 diabetes was confirmed by two OGTTs. Cardiovascular outcome was measured as incident CVD or CVD mortality. Multivariate log-binomial regression models were used to predict diabetes, CVD, and CVD mortality at 10 years. Receiver operating characteristic curves compared predictive values of A1C, IGT, and IFG.

RESULTS

Incidence of diabetes during the follow-up was 17.1%. Two of three of the cases of newly diagnosed diabetes were predicted by a raise in ≥1 of the markers. Elevated A1C, IGT, or IFG preceded diabetes in 32.8, 40.6, and 21.9%, respectively. CVD was predicted by an intermediate and diabetic range of 2-h glucose but only by diabetic A1C levels in women.

CONCLUSIONS

A1C predicted 10-year risk of type 2 diabetes at a range of A1C 5.7–6.4% but CVD only in women at A1C ≥6.5%.Early detection of high risk for type 2 diabetes is fundamental for prevention of diabetes and associated cardiovascular complications. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are currently used for diagnosis of high-risk glucose levels below the diabetic range. The International Expert Committee proposed A1C ≥6.5% as a diagnostic tool for diabetes in 2009 (1) and in January 2010 an intermediate range of A1C 5.7–6.4% (elevated A1C) was proposed by the American Diabetes Association (ADA) to detect individuals at high risk for developing type 2 diabetes (2).To date, however, limited data exist to support the use of A1C in predicting type 2 diabetes (3–8). Importantly, the long-term predictive power of elevated A1C as defined above has not yet been investigated. Previous data on the association between A1C and incident type 2 diabetes in unselected populations have relied on self-reporting, fasting glucose measurements, and use of antidiabetes medication to determine the outcomes. An oral glucose tolerance test (OGTT) has not been used to determine the outcome (3–8).Deterioration of glucose homeostasis reflects a continuum of glycemia, some of which is reversible if detected early (9,10). Importantly, the risk of cardiovascular disease is increased already before glycemia reaches the levels of diabetes, and 2-h glucose appears to be a better predictor of cardiovascular disease (CVD) than fasting glucose (11). Recently, A1C was shown to be a better predictor of CVD than fasting glucose (12).Data directly comparing 2-h glucose and A1C as long-term predictors of new-onset cardiovascular disease are scarce, and results are controversial (13,14). Therefore, we compared A1C, 2-h glucose, and fasting glucose as predictors of type 2 diabetes, CVD, and CVD mortality during a prospective population-based study with a 10-year follow-up.     

Health-related quality of life among German youths with early-onset and long-duration type 1 diabetes

OBJECTIVE

To evaluate self- and parent reports of general health status and health-related quality of life (QoL) in children and adolescents with early-onset and long-lasting type 1 diabetes compared with the general population in Germany.

RESEARCH DESIGN AND METHODS

A total of 629 subjects aged 11 to 17 years, with a type 1 diabetes onset occurring from age 0 to 4 years during the years 1993–1999, and their parents, completed questionnaires, including the generic KINDL-R Questionnaire for Measuring Health-Related Quality of Life in Children and Adolescents, revised version, to assess QoL. The comparison group (n = 6,813) was a representative sample from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) study. Regression analyses were conducted using sociodemographic and health-related covariates.

RESULTS

Intensified insulin therapy was used to treat 93% of children and adolescents with type 1 diabetes. They reported “excellent” general health as often as peers (adjusted OR 0.83 [95% CI 0.66–1.04] for an “excellent” rating), but the parent-rated general health was worse than that in the general population (OR 0.60 [0.48–0.74]). The patients reported increased self-esteem (adjusted difference β = 4.39 [SE 0.82]; P < 0.001) and well-being at school (β = 3.41 [0.77]; P < 0.001) but lower well-being within their families (β = –2.42 [0.80]; P = 0.002). The self- and parent-reported total QoL did not differ between the patient group and the general population. The adjusted difference (SE) between the two samples in total QoL was β = 0.89 (0.52; P = 0.087) in the self-reports and β = –0.98 (0.53; P = 0.066) in the parent-reports.

CONCLUSIONS

Compared with the general population, the QoL and general health status were not impaired among those aged 11–17 years with early-onset type 1 diabetes, despite the challenges of modern therapy.Early-onset type 1 diabetes is a chronic metabolic disorder with a continuously rising incidence in Germany and many other countries, in particular among 0- to 4-year-old children, with a predicted doubling of cases in Europe between 2005 and 2020 (1,2). To ensure normal physical growth and development and to prevent acute and late diabetes complications, life-long continuous self-management is necessary. Complex treatment regimens (3) and awareness of possible diabetes complications can affect the lives of patients and their families and cause psychosocial problems (4). In turn, adverse psychosocial conditions may increase the risk of poor self-management and deterioration of glycemic control (5,6).A major goal of pediatric diabetes care is to achieve near-normal glycemic control without a significant impairment in the quality of life (QoL). The health-related QoL has been increasingly recognized as an important health indicator for children in the general population and in those with chronic conditions, such as type 1 diabetes (7). Wallander et al. (8) defined QoL as well-being in multiple domains of life considered salient in one’s culture and time. By using QoL measurements with a generic approach, direct comparisons of populations with different states of health are possible (8). It is recommended that self-reported QoL data be complemented by proxy-ratings. Parents’ perceptions of their children’s disease and the effects of the disease on daily life can provide important complementary information (9–11). The World Health Organization recommends the self-assessment of health by a very general and simple question as a principal indicator (12).Several studies have already analyzed the QoL of youths with type 1 diabetes compared with peers, and findings were not consistent (13–21). Previous studies that used the Pediatric Quality of Life Inventory (PedsQL) to measure generic QoL and compared the type 1 diabetic sample with healthy peers observed worse QoL reported by patients (13), by both patients and parents (14), or only by parents (15,16). Studies that analyzed generic QoL measured by the Questionnaire for Measuring Health-Related Quality of Life in Children and Adolescents, revised version (KINDL-R) did not observe impaired self-reported QoL among youths with type 1 diabetes (17,18). Another study reported an even higher total QoL (measured by a self-designed questionnaire) among youths with type 1 diabetes than among healthy control subjects (19). In studies using the Child Health Questionnaire, youths with type 1 diabetes did not differ from peers, except for a lower rating on the general health scale (20,21), but parent-reported functional health and well-being was worse (21). The QoL of youths with early-onset diabetes, beginning between the ages of 0 and 4 years and already continuing for 10 or more years, is largely unexplored.The aim of this study was to compare the self- and proxy-reported general health status and multidimensional generic QoL in youths with early-onset and long-lasting type 1 diabetes with data from representative normal peers.     

Long-Term Cardiovascular Risk in Type 2 Diabetic Compared With Nondiabetic First Acute Myocardial Infarction Patients: A population-based cohort study in southern Europe

OBJECTIVE

The aim of this study was to determine whether long-term cardiovascular risk differs in type 2 diabetic patients compared with first acute myocardial infarction patients in a Mediterranean region, considering therapy, diabetes duration, and glycemic control.

RESEARCH DESIGN AND METHODS

A prospective population-based cohort study with 10-year follow-up was performed in 4,410 patients aged 30–74 years: 2,260 with type 2 diabetes without coronary heart disease recruited in 53 primary health care centers and 2,150 with first acute myocardial infarction without diabetes recruited in 10 hospitals. We compared coronary heart disease incidence and cardiovascular mortality rates in myocardial infarction patients and diabetic patients, including subgroups by diabetes treatment, duration, and A1C.

RESULTS

The adjusted hazard ratios (HRs) for 10-year coronary heart disease incidence and for cardiovascular mortality were significantly lower in men and women with diabetes than in myocardial infarction patients: HR 0.54 (95% CI 0.45–0.66) and 0.28 (0.21–0.37) and 0.26 (0.19–0.36) and 0.16 (0.10–0.26), respectively. All diabetic patient subgroups had significantly fewer events than myocardial infarction patients: the HR of cardiovascular mortality ranged from 0.15 (0.09–0.26) to 0.36 (0.24–0.54) and that of coronary heart disease incidence ranged from 0.34 (0.26–0.46) to 0.56 (0.43–0.72).

CONCLUSIONS

Lower long-term cardiovascular risk was found in type 2 diabetic and all subgroups analyzed compared with myocardial infarction patients. These results do not support equivalence in coronary disease risk for diabetic and myocardial infarction patients.The prevalence of diabetes is reaching epidemic proportions in developed countries (1). For example, the U.S. has 18 million diabetic patients, Spain has >2 million diabetic patients, and management of the disease costs >$132 and >$3.3 billion per year, respectively (2).Some studies (3–5), several of them with great influence on important guidelines for cardiovascular prevention (3), suggest that the cardiovascular risk of diabetic patients is similar to that of coronary heart disease secondary prevention patients. Other reports, however, do not confirm these observations (6–10).Part of the discrepancy may stem from differences in the duration of diabetes, type of treatment, and baseline glucose control of diabetic patients included in the studies (3–5). These limit comparability, given the fact that time of evolution and treatment required to attain appropriate glycemic control are key determinants of prognosis (10–16).Among population-based cohort studies that compared the prognosis of diabetic patients with that of myocardial infarction patients without diabetes (3–10), only two analyzed the role of diabetes duration (11,12). Even these studies did not include unstable angina among the end points and risk was not stratified by type of treatment. To our knowledge, the effect of type 2 diabetes on coronary heart disease incidence has barely been studied in southern Europe, a region known for low cardiovascular mortality (17). The aim of this study was to determine whether long-term cardiovascular risk differed between type 2 diabetic patients and first acute myocardial infarction patients and to assess the influence of diabetes duration, type of treatment, and glycemic control at baseline.     

��-Cell�CMediated Signaling Predominates Over Direct ��-Cell Signaling in the Regulation of Glucagon Secretion in Humans

OBJECTIVE

Given evidence of both indirect and direct signaling, we tested the hypothesis that increased β-cell–mediated signaling of α-cells negates direct α-cell signaling in the regulation of glucagon secretion in humans.

RESEARCH DESIGN AND METHODS

We measured plasma glucagon concentrations before and after ingestion of a formula mixed meal and, on a separate occasion, ingestion of the sulfonylurea glimepiride in 24 basal insulin-infused, demonstrably β-cell–deficient patients with type 1 diabetes and 20 nondiabetic, demonstrably β-cell–sufficient individuals; the latter were infused with glucose to prevent hypoglycemia after glimepiride.

RESULTS

After the mixed meal, plasma glucagon concentrations increased from 22 ± 1 pmol/l (78 ± 4 pg/ml) to 30 ± 2 pmol/l (103 ± 7 pg/ml) in the patients with type 1 diabetes but were unchanged from 27 ± 1 pmol/l (93 ± 3 pg/ml) to 26 ± 1 pmol/l (89 ± 3 pg/ml) in the nondiabetic individuals (P < 0.0001). After glimepiride, plasma glucagon concentrations increased from 24 ± 1 pmol/l (83 ± 4 pg/ml) to 26 ± 1 pmol/l (91 ± 4 pg/ml) in the patients with type 1 diabetes and decreased from 28 ± 1 pmol/l (97 ± 5 pg/ml) to 24 ± 1 pmol/l (82 ± 4 pg/ml) in the nondiabetic individuals (P < 0.0001). Thus, in the presence of both β-cell and α-cell secretory stimuli (increased amino acid and glucose levels, a sulfonylurea) glucagon secretion was prevented when β-cell secretion was sufficient but not when β-cell secretion was deficient.

CONCLUSIONS

These data indicate that, among the array of signals, indirect reciprocal β-cell–mediated signaling predominates over direct α-cell signaling in the regulation of glucagon secretion in humans.The regulation of pancreatic islet α-cell glucagon secretion is complex (1–10). It involves direct signaling of α-cells (1) and indirect signaling of α-cells by β-cell (2–6) and δ-cell (7) secretory products, the autonomic nervous system (8,9), and gut incretins (10).Appropriate glucagon secretory responses occur from the perfused pancreas (3,5) and perifused islets (2). Low plasma glucose concentrations stimulate glucagon secretion from the transplanted (i.e., denervated) human pancreas (11) and the denervated dog pancreas (12). Therefore, we have focused on the intraislet regulation of glucagon secretion. Furthermore, because selective destruction of β-cells results in loss of the glucagon response to hypoglycemia in type 1 diabetes (13), and partial reduction of the β-cell mass in minipigs results in impaired postprandial suppression of glucagon secretion (14), we have focused on the role of β-cell–mediated signaling in the regulation of glucagon secretion.Findings from studies of the perfused rat (3,4) and human (5) pancreas, rats in vivo (6), rat islets (2), isolated rat α-cells (2), and humans (15–18) have been interpreted to indicate that a β-cell secretory product or products tonically restrains basal α-cell glucagon secretion during euglycemia and that a decrease in β-cell secretion, coupled with low glucose concentrations at the α-cells, signals an increase in glucagon secretion in response to hypoglycemia. Parenthetically, the relative roles of the candidate β-cell secretory products (insulin, zinc, γ-aminobutyric acid, and amylin, among others) (2) that normally restrain α-cell glucagon secretion remain to be determined. However, that interpretation rests, in part, on results of studies in isolated rat α-cells (2), which are debated (1), and on the evidence that the islet microcirculation flows from β-cells to α-cells to δ-cells (4), which is also debated (19). Furthermore, it does not address the plausible possibility that a decrease in intraislet δ-cell somatostatin secretion might also signal an increase in α-cell glucagon secretion during hypoglycemia (7).Given that interpretation, it follows that an increase in β-cell secretion would signal a decrease in glucagon secretion in the postprandial state (14). The concept is an interplay of indirect reciprocal β-cell–mediated signaling of α-cells and of direct α-cell signaling in the regulation of glucagon secretion.There is, in our view, compelling evidence that, among other mechanisms, both indirect reciprocal β-cell–mediated signaling of α-cells (2–6) and direct α-cell signaling (1) are involved in the regulation of glucagon secretion by nutrients, hormones, neurotransmitters, and drugs. Given that premise, we posed the question: Which of these predominates in humans? Accordingly, we tested the hypothesis that increased β-cell–mediated signaling of α-cells negates direct α-cell signaling in the regulation of glucagon secretion in humans. To do so, we measured plasma glucagon responses to ingestion of a mixed meal and, on a separate occasion, to ingestion of the sulfonylurea glimepiride in patients with type 1 diabetes and in nondiabetic individuals. We conceptualized patients with type 1 diabetes as a model of α-cells isolated from β-cells because their β-cells had been destroyed but they have functioning α-cells. (Their α-cells are not, of course, isolated from other islet cells, including δ-cells.) Increased plasma amino acid and glucose levels after a mixed meal and sulfonylureas normally stimulate β-cell secretion; increased plasma amino acid and perhaps glucose (2) levels after a mixed meal and sulfonylureas (1) stimulate α-cell secretion. Our hypothesis predicts that such factors that normally stimulate both β-cells and α-cells would stimulate glucagon secretion in patients with type 1 diabetes but not in nondiabetic individuals, i.e., in the virtual absence and the presence of β-cell function, respectively. Indeed, a mixed meal (20,21) and the secretagogues tolbutamide (22), glyburide (23), and repaglinide (23) have been reported to raise plasma glucagon concentrations in patients with type 1 diabetes, but all of those studies lacked nondiabetic control subjects.     

Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children

OBJECTIVE

To determine the frequency of newly diagnosed diabetic children with first- and second-degree relatives affected by type 1 diabetes and to characterize the effects of this positive family history on clinical markers, signs of β-cell autoimmunity, and HLA genotype in the index case.

RESEARCH DESIGN AND METHODS

Children (n = 1,488) with type 1 diabetes diagnosed under 15 years of age were included in a cross-sectional study from the Finnish Pediatric Diabetes Register. Data on family history of diabetes and metabolic decompensation at diagnosis were collected using a questionnaire. Antibodies to β-cell autoantigens (islet cell antibodies, insulin autoantibodies, GAD antibodies, and antibodies to the islet antigen 2 molecule) and HLA genotypes were analyzed.

RESULTS

A total of 12.2% of the subjects had a first-degree relative with type 1 diabetes (father 6.2%, mother 3.2%, and sibling 4.8%) and 11.9% had an affected second-degree relative. Children without affected relatives had lower pH (P < 0.001), higher plasma glucose (P < 0.001) and β-hydroxybutyrate concentrations (P < 0.001), a higher rate of impaired consciousness (P = 0.02), and greater weight loss (P < 0.001). There were no differences in signs of β-cell autoimmunity. The familial cases carried the HLA DR4-DQ8 haplotype more frequently than sporadic cases (74.0 vs. 67.0%, P = 0.02).

CONCLUSIONS

When the extended family history of type 1 diabetes is considered, the proportion of sporadic diabetes cases may be reduced to <80%. A positive family history for type 1 diabetes associates with a less severe metabolic decompensation at diagnosis, even when only second-degree relatives are affected. Autoantibody profiles are similar in familial and sporadic type 1 diabetes, suggesting similar pathogenetic mechanisms.Familial clustering of type 1 diabetes is a conspicuous feature; the risk of developing type 1 diabetes is 8–15-fold higher in first-degree relatives (1–6) and twofold in second-degree relatives (1,7). Despite this, the vast majority of children are diagnosed with the sporadic form of diabetes. The proportion of children with an affected first-degree relative at the time of diagnosis is ∼10–12% (7–13), and after decades of follow-up, this frequency increases to >20% (8,14,15). Fathers transmit the disease to their offspring more often than mothers (3,16). Accordingly, at diagnosis, 4–7% of children have a father with type 1 diabetes whereas only 1.5–3% have an affected mother (7–12,17). Fewer reports exist on type 1 diabetes in the extended family. Depending on the definition of second-degree relatives and length of time from the diagnosis of the index case, 5–16% of children with type 1 diabetes have an affected second-degree relative (1,5,11,17–19).Familial and sporadic type 1 diabetes have been suggested to differ in terms of pathogenetic mechanisms (20,21). The risk-associated HLA genotypes have been observed more often in familial type 1 diabetes (8,20,22,23), although not all studies have found significant differences (24). Two studies have noticed no differences in diabetes-associated autoantibodies, e.g., insulin autoantibodies (IAAs) (8), GAD antibodies (GADAs) (8), or islet cell antibodies (ICAs) (8,20). A recent study from Israel reported, however, higher frequencies of IAAs and a higher number of positive antibody responses among familial cases (13). In families with prior experience of type 1 diabetes in a first-degree relative, the clinical status of the child at diagnosis is less severe (8,13,21).Data on the possible pathogenetic differences between familial and sporadic type 1 diabetes are still inconsistent and based on a positive family history in first-degree relatives only. To further our understanding of familial clustering of type 1 diabetes, we used data from the large, nationwide Finnish Pediatric Diabetes Register for a cross-sectional observational study. Since the knowledge of the effects of an extended family history on the diabetes of the index case is lacking, we included information on second-degree relatives (grandparents and siblings of parents). β-Cell autoimmunity, metabolic decompensation at diagnosis, and HLA genetics were compared in children with familial or sporadic type 1 diabetes. We postulated to see a stronger genetic susceptibility to type 1 diabetes and a milder metabolic decompensation in children with a positive family history for type 1 diabetes, whereas no differences were expected in the autoantibody profile.     

Prevalence and Correlates of Latent Autoimmune Diabetes in Adults in Tianjin, China: A population-based cross-sectional study

OBJECTIVE

Data on latent autoimmune diabetes in adults (LADA) from population-based studies are sparse. We sought to investigate the prevalence and correlates of LADA.

RESEARCH DESIGN AND METHODS

A total of 8,109 participants, who were aged ≥15 years and living in Tianjin, China, were assessed to identify individuals with type 2 diabetes (American Diabetes Association Criteria, 1997) and further to detect patients with LADA. LADA was ascertained by 1) the presence of type 2 diabetes and age ≥35 years, 2) the lack of a requirement for insulin at least 6 months after the diagnosis of type 2 diabetes, and 3) serum GAD antibody positivity. Data were analyzed using multinomial logistic regression with adjustment for potential confounders.

RESULTS

Of all participants, 498 (6.1%) were patients with type 2 diabetes. Of them, 46 (9.2%) were found to have LADA. The prevalence of LADA was 0.6% (46 of 8,109), and tended to increase with age up to 50–59 years in all participants. The odds ratios (95% CI) of LADA related to hypertension, family history of diabetes, waist-to-hip ratio ≥0.85, and major stressful events were 1.93 (1.02–3.65), 17.59 (9.08–34.06), 5.37 (2.31–12.49), and 4.09 (1.75–9.52), respectively.

CONCLUSIONS

The prevalence of LADA is ∼9% in patients with type 2 diabetes. Hypertension, family history of diabetes, central obesity, and major stressful events may be associated with the occurrence of LADA.Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes and is characterized by diabetes-associated autoantibody positivity (1). Patients with LADA have an insidious onset of hyperglycemia and clinical presentation similar to that of type 2 diabetes at onset (2,3). Epidemiological studies suggest that LADA may account for 2–12% of all cases of diabetes (4).The prevalence of LADA in western countries varies from 2.8 to 10% in patients with type 2 diabetes (5–8). The Diabetes Outcomes Progression Trial recently reported that GAD antibody (GADA) positivity is 4.2% in North America and 3.7% in Europe among individuals with type 2 diabetes (9). In China, two clinical studies have shown that the estimated prevalence of LADA in patients with type 2 diabetes is ∼7% (10,11). The etiology of LADA is unclear, and it is not known whether LADA is due to the same underlying disease process as childhood type 1 diabetes. A recent study has suggested that the patients with LADA share genetic features with both type 1 and type 2 diabetic patients (12). In addition, several studies have reported that metabolic disorders, such as hypertension and obesity, and a family history of diabetes are associated with the risk of LADA (10,13,14).Accumulating clinical evidence has shown significant overlap between type 1 and type 2 diabetes. The disease process in patients with classic type 1 diabetes is believed to be autoimmune in nature, whereas the disease process in classic type 2 diabetes is not. The treatment for patients with LADA may need to be different from that used for patients with type 2 diabetes (15). Because LADA is frequently misdiagnosed as type 2 diabetes, identification of LADA is of clinical importance. In this population-based cross-sectional study, we sought to investigate the prevalence of LADA and further to explore whether familial, vascular, and psychosocial factors are associated with the occurrence of LADA.     

Impact of Metabolic Syndrome Compared With Impaired Fasting Glucose on the Development of Type 2 Diabetes in a General Japanese Population: The Hisayama study

OBJECTIVE

We examined whether metabolic syndrome predicts incident type 2 diabetes more effectively than impaired fasting glucose (IFG) in a general Japanese population.

RESEARCH DESIGN AND METHODS

A total of 1,935 nondiabetic subjects aged 40–79 years were followed-up prospectively for a mean of 11.8 years.

RESULTS

During the follow-up, 286 subjects developed type 2 diabetes. Compared with those without metabolic syndrome, the multivariate-adjusted hazard ratio (HR) for incident type 2 diabetes was significantly higher in subjects of both sexes with metabolic syndrome, even after adjustment for confounding factors, age, family history of diabetes, total cholesterol, alcohol intake, smoking habits, and regular exercise (men: HR 2.58 [95% CI 1.85–3.59]; women: 3.69 [2.58–5.27]). The multivariate-adjusted HR of metabolic syndrome for type 2 diabetes was slightly lower in men and similar in women compared with that of IFG. The multivariate-adjusted HR for type 2 diabetes rose progressively as the number of metabolic syndrome components increased in both subjects with and without IFG. In stratified analysis, the multivariate-adjusted risk of type 2 diabetes was significantly higher in subjects with metabolic syndrome alone (2.37 [1.45–3.88]) or IFG alone (3.49 [2.57–4.74]) and markedly increased in subjects with both metabolic syndrome and IFG (6.76 [4.75–9.61]) than in subjects with neither metabolic syndrome nor IFG. Furthermore, the multivariate-adjusted risk for type 2 diabetes was also significantly higher in subjects with both metabolic syndrome and IFG than in those with either one alone (both P < 0.001).

CONCLUSIONS

Our findings suggest that metabolic syndrome significantly increases the risk of incident type 2 diabetes, independent of IFG, and is therefore a valuable tool to identify individuals at high risk of type 2 diabetes.Metabolic syndrome consists of a clustering of cardiovascular risk factors, such as central obesity, elevated blood pressure, glucose intolerance, and dyslipidemia, and individuals with this condition have an elevated risk of developing cardiovascular diseases (1–5) and type 2 diabetes in different ethnic populations (1–4,6–11). Thus, the concept of metabolic syndrome could be used to reduce the incidence of these diseases worldwide. However, a number of experts in the field of diabetes have questioned whether the idea of metabolic syndrome is useful and valuable (12–14). Because all of the criteria sets for metabolic syndrome have included the component of impaired fasting glucose (IFG), which is a powerful predictor of type 2 diabetes, detractors have questioned whether the more complex definition of metabolic syndrome is better than a simple measurement of fasting plasma glucose (FPG). However, reported findings concerning this issue are controversial: a cohort study has shown that the ability of metabolic syndrome to predict type 2 diabetes was superior to that of IFG alone (3), whereas in other studies, the value of metabolic syndrome was comparable or inferior to that of IFG alone (2,6,7). Furthermore, most of these epidemiological studies were performed in Western populations, and this subject has not been assessed sufficiently in Asian populations.The purpose of the present study was to investigate the association between metabolic syndrome and the development of type 2 diabetes in a prospective study of a defined Japanese population, taking into account comprehensive risk factors. In addition, we compared which of the two measures, metabolic syndrome or IFG, better predicted incident type 2 diabetes.     

Improved metabolic control in children and adolescents with type 1 diabetes: a trend analysis using prospective multicenter data from Germany and Austria

OBJECTIVE

To investigate the temporal trend of metabolic control and potential predictors in German and Austrian children and adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS

This study is based on a large, multicenter database for prospective longitudinal documentation of diabetes care in Germany and Austria. Data from 30,708 patients documented in 305 diabetes centers between 1995 and 2009 were analyzed. Generalized linear mixed regression models were used to adjust trend analysis for relevant confounders.

RESULTS

Unadjusted mean HbA_1c decreased from 8.7 ± 1.8% in 1995 to 8.1 ± 1.5% in 2009. In multiple regression analysis, treatment year, age, sex, diabetes duration, migration background, BMI-SDS, and daily insulin dose were significant predictors of metabolic control (P < 0.001). After multiple adjustment, mean HbA_1c decreased significantly by 0.038% per year (95% CI 0.032–0.043%), average odds ratio (OR) per year for HbA_1c >7.5% (>9.0%) was 0.969 (95% CI 0.961–0.977) (0.948, 95% CI 0.941–0.956). Intensified insulin regimen was associated with lower frequency of poor metabolic control (HbA_1c >9%; P = 0.005) but not with average HbA_1c (P = 0.797). Rate of severe hypoglycemia and hypoglycemic coma decreased significantly (relative risk [RR] per year 0.948, 95% CI 0.918–0.979; RR 0.917, 95% CI 0.885–0.950) over the study period. Diabetic ketoacidosis rate showed no significant variation over time.

CONCLUSIONS

This study showed a significant improvement in metabolic control in children and adolescents with type 1 diabetes during the past decade and a simultaneous decrease in hypoglycemic events. The improvement was not completely explained by changes in the mode of insulin treatment. Other factors such as improved patient education may have accounted for the observed trend.The Diabetes Control and Complications Trial (DCCT) showed that improved metabolic control reduces the risk of long-term complications in both adult and adolescent patients with type 1 diabetes (1,2). The observational follow-up study of the DCCT (the Epidemiology of Diabetes Interventions and Complications [EDIC] study) further proved that good glycemic control had persistent beneficial effects on long-term complications (3). Based on the results of the DCCT/EDIC study, it was recommended to optimize glycemic control as early and close to normal as possible in all patients with type 1 diabetes in order to prevent development and progression of microvascular complications.Diabetes treatment has been intensified in pediatric and adolescent patients during the past 15 years. Insulin therapy has changed from twice-daily injection regimen to intensified therapy with multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII). This has been reported from single-center and multicenter studies (4–10). In the 1990s, mainly an increased use of MDI was observed, whereas since 2000, pump therapy increased considerably, paralleled by a decrease in MDI therapy (11). With the intensification of insulin regimen, the frequency of daily self-monitoring of blood glucose (SMBG) increased continuously (5,10–12), as close glucose monitoring is a precondition for intensified insulin therapy with an appropriate dose adjustment. Likewise, the use of short-acting insulin analogs has continuously increased since the mid-1990s and the use of long-acting analogs since 2000 (4,5,10).Despite these far-ranging changes in diabetes therapy, the anticipated improvement in metabolic control in children and adolescents with type 1 diabetes has not been achieved in all settings. The multicenter Hvidoere studies did not observe any improvement in glycemic control during 1995–2005 (6–8). Other studies, however, reported a significant decrease in average HbA_1c level over the past two decades (4,5,10,11,13). Concordantly, several studies indicated a notable increase in the proportion of children and adolescents with good metabolic control (HbA_1c <7.5 or <8%) over the past years (11,13).In the DCCT study, the tradeoff with intensified insulin therapy was a marked increase in episodes of severe hypoglycemia (2). Several studies reported a higher hypoglycemia risk with lower HbA_1c level (4,6,7,10,14), but others did not (15,16). Results on the trend of severe hypoglycemic events over the past 15 years are also inconsistent (4,5,8,9,11).The aim of this study was to give a current update on the temporal trend of metabolic control in German and Austrian children and adolescents over the past 15 years (1995–2009), to identify potential determinants of metabolic control, and to analyze the simultaneous trend of severe hypoglycemic and diabetic ketoacidotic events.