Plasma Industrial and Ruminant Trans Fatty Acids and Incident Type 2 Diabetes in the EPIC-Potsdam Cohort

OBJECTIVEAlthough dietary intake of trans fatty acid (TFA) is a major public health concern because of the associated increase in the risk of cardiovascular events, it remains unclear whether TFAs also influence risk of type 2 diabetes (T2D) and whether industrial TFAs (iTFAs) and ruminant TFAs (rTFAs) exert the same effect on health.RESEARCH DESIGN AND METHODSTo investigate the relationship of 7 rTFAs and iTFAs, including 2 conjugated linoleic acids (CLAs), plasma phospholipid TFAs were measured in a case-cohort study nested within the European Prospective Investigation Into Cancer and Nutrition–Potsdam cohort. The analytical sample was a random subsample (n = 1,248) and incident cases of T2D (n = 801) over a median follow-up of 6.5 years. Using multivariable Cox regression models, we examined associations of TFAs with incident T2D.RESULTSThe TFA subtypes were intercorrelated with each other, with other fatty acids, and with different food sources. After controlling for other TFAs, the iTFAs (18:1n-6t, 18:1n-9t, 18:2n-6,9t) were not associated with diabetes risk. Some rTFA subtypes were inversely associated with diabetes risk: vaccenic acid (18:1n-7t; hazard ratio [HR] per SD 0.72; 95% CI 0.58–0.89) and t10c12-CLA (HR per SD 0.81; 95% CI 0.70–0.94), whereas c9t11-CLA was positively associated (HR per SD 1.39; 95% CI 1.19–1.62). Trans-palmitoleic acid (16:1n-7t) was not associated with diabetes risk when adjusting for the other TFAs (HR per SD 1.08; 95% CI 0.88–1.31).CONCLUSIONSThe TFAs’ conformation plays an essential role in their relationship to diabetes risk. rTFA subtypes may have opposing relationships to diabetes risk. Previous observations for reduced diabetes risk with higher levels of circulating trans-palmitoleic acid are likely due to confounding.     

Risk Factors for Incident Fracture in Older Adults With Type 2 Diabetes: The Framingham Heart Study

OBJECTIVETo identify risk factors for fracture in type 2 diabetes.RESEARCH DESIGN AND METHODSThis prospective study included members of the Framingham Original and Offspring Cohorts. Type 2 diabetes was defined as fasting plasma glucose >125 mg/dL or use of type 2 diabetes therapy. We used repeated-measures Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% CIs for associations between potential predictors and incidence of fragility fracture.RESULTSParticipants included 793 individuals with type 2 diabetes. Mean ± SD age was 70 ± 10 years; 45% were women. A total of 106 incident fractures occurred over 1,437 observation follow-up intervals. Fracture incidence increased with age (adjusted HRs 1.00, 1.44 [95% CI 0.65, 3.16], and 2.40 [1.14, 5.04] for <60, 60–70, and >70 years, respectively; P_trend = 0.02), female sex (2.23 [1.26, 3.95]), HbA_1c (1.00, 2.10 [1.17, 3.75], and 1.29 [0.69, 2.41] for 4.45–6.46% [25–47 mmol/mol], 6.50–7.49% [48–58 mmol/mol], and 7.50–13.86% [58–128 mmol/mol]; P_trend =0.03), falls in past year (1.00, 1.87 [0.82, 4.28], and 3.29 [1.34, 8.09] for no falls, one fall, and two or more falls; P_trend =0.03), fracture history (2.05 [1.34, 3.12]), and lower grip strength (0.82 [0.69, 0.99] per 5-kg increase). Femoral neck bone mineral density, BMI, smoking, physical function, chronic diseases, medications, and physical function were not associated with fracture incidence.CONCLUSIONSPrior falls, fractures, low grip strength, and elevated HbA_1c are risk factors for fractures in older adults with type 2 diabetes. Evaluation of these factors may improve opportunities for early intervention and reduce fractures in this high-risk group.     

Relationship Between Obesity and Incident Diabetes in Middle-Aged and Older Japanese Adults: The Ibaraki Prefectural Health Study

OBJECTIVE: To investigate the age-specific relationship between body mass index (BMI) and risk of diabetes in a Japanese general population.PARTICIPANTS AND METHODS: A cohort of Japanese men (N=19,926) and women (N=41,489) (aged 40-79 years) who under went community-based health checkups in 1993 and were free of diabetes was followed up by annual examinations with measurement of blood glucose concentrations until the end of 2006. Incident diabetes mellitus was defined as a blood glucose concentration of 126 mg/dL or greater under fasting conditions, 200 mg/dL or greater under nonfasting conditions, or diabetic medication use at baseline. Hazard ratios (HRs) for diabetes according to BMI were estimated using a Cox proportional hazard model. The model was adjusted for possible confounding variables.RESULTS: A total of 4429 participants (7.2%) developed diabetes (2065 men and 2364 women) during a mean follow-up of 5.5 years. Compared with those with a BMI of less than 25.0, the multivariate HRs for diabetes among participants with a BMI of 30.0 or greater were 1.40 (95% confidence interval [CI], 0.89-2.20) for men aged 40 to 59 years and 1.26 (95% CI, 0.81-1.96) for men aged 60 to 79 years (P=.002 for interaction). The HRs were 2.50 (95% CI, 2.01-3.11) for women aged 40 to 59 years and 1.80 (95% CI, 1.41-2.30) for women aged 60 to 79 years (P=.04 for interaction).CONCLUSION: The effect of obesity on the risk of diabetes is greater for middle-aged than for older adults.BMI = body mass index; CI = confidence interval; HR = hazard ratioDiabetes mellitus is one of the major public health problems in Western countries and in Japan as a risk factor of cardiovascular diseases.^1,2 Many previous prospective studies have shown that obesity or being overweight is related to the risk of diabetes mellitus.^3-11 The Health Professionals'' Follow-up Study⁸ of 51,529 US male dentists, veterinarians, osteopaths, podiatrists, optometrists, and pharmacists aged 40 to 75 years reported that the risk of diabetes mellitus increased continuously with increasing body mass index (BMI; calculated as the weight in kilograms divided by height in meters squared) among men with a BMI of 23 or greater. The Nurses'' Health Study⁶ of 113,861 US female nurses aged 30 to 55 years also reported similar results among women with a BMI of 22 or greater. Because treating long-term diabetes mellitus is costly, the best approach to control diabetes is primary prevention. Examining the modifiable risk factors for diabetes mellitus, including obesity, is important because of its public health implications.The relationship between obesity and diabetes mellitus has been reported to be age-dependent. A recent meta-analysis has shown an age-dependent relationship between BMI and the incidence of diabetes mellitus throughout the entire Asia-Pacific region.¹² However, this age-dependent relationship has not been extensively studied in a large cohort of the general population in Japan only. Clarification of this issue may help by implementation of more effective public health and clinical efforts aimed at primary prevention of diabetes mellitus via weight control. The increasing prevalence of diabetes mellitus in all age groups in Japan highlights the need for such data. The purpose of the current study was to investigate whether aging affects the relationship between the degree of obesity and incident diabetes mellitus in a large Japanese cohort.     

Sex-Specific Association of Fetuin-A With Type 2 Diabetes in Older Community-Dwelling Adults: The Rancho Bernardo Study

OBJECTIVE

This study evaluated the sex-specific association of plasma fetuin-A levels with prevalent and incident type 2 diabetes in community-dwelling older adults.

RESEARCH DESIGN AND METHODS

Participants were 684 men and 1,058 women (median age, 71 years) whose fetuin-A levels, diabetes prevalence, and diabetes risk factors were evaluated in 1992–1996. The participants were followed for incident diabetes through 2010 (median follow-up, 9 years).

RESULTS

Women with impaired glucose tolerance had elevated fetuin-A levels compared with women with normal glucose tolerance (P = 0.019), but fetuin-A levels were not elevated in women with impaired fasting glucose. Fetuin-A did not vary by glucose tolerance status in men. There were significant interactions of fetuin-A by sex for prevalent (P = 0.007) and incident (P = 0.020) diabetes. For women, each SD (0.10 g/L) higher fetuin-A level was associated with a higher odds of prevalent diabetes (odds ratio [OR] 1.79, 95% CI 1.47–2.17) and greater risk of incident diabetes (hazard ratio [HR] 1.66, 95% CI 1.18–2.34), adjusting for age and estrogen therapy. These associations were not materially altered by adjustment for diabetes risk factors but were attenuated by adjusting for postchallenge glucose levels. Among men, although positive associations with prevalent (OR 1.15 [0.94–1.41]) and incident (HR 1.24 [0.93–1.65]) diabetes were suggested in age-adjusted models, risk estimates attenuated to one after multivariable adjustment.

CONCLUSIONS

Higher fetuin-A concentrations were independently associated with an increased risk of developing type 2 diabetes in older women but were not related to diabetes risk in older men. Fetuin-A may provide novel insights into mechanisms underlying sex differences in glucose homeostasis and diabetes risk in old age.Type 2 diabetes is now epidemic. In the U.S., there are 1.5 million incident cases annually, and the prevalence in 2011 was almost 26 million (1). Type 2 diabetes is a heterogeneous disorder that results from the complex interplay of genetic susceptibility and lifestyle choices, leading to insulin resistance and impaired β-cell function (2). Available data suggest that glucose regulation and the pathophysiology of diabetes show sex differences that may be particularly relevant in older adults (2–5). For example, a markedly higher prevalence of postchallenge hyperglycemia has been reported in older women compared with that in older men, whereas fasting hyperglycemia is more common in older men than in older women (6–10).Fetuin-A is a protein secreted primarily by the liver that regulates insulin signaling (11) and circulates in higher concentrations in women than in men (12–15). Only two proteins are known to bind directly to the extracellular domain of the insulin receptor: insulin and fetuin-A. Experimental evidence indicates that fetuin-A binding inhibits the insulin receptor tyrosine kinase (16) and induces insulin resistance in skeletal muscle and fat (11). In epidemiologic studies, we and others have shown that higher fetuin-A levels are associated with the development of type 2 diabetes independent of established markers of insulin resistance and diabetes risk factors (13,14,17,18).To date, no epidemiologic studies have comprehensively investigated the association of fetuin-A with measures of glucose homeostasis and prevalent and incident diabetes among older men and women from the same population. Examining associations at various stages of the pathway to diabetes may provide novel insights into the biological interaction between this unique liver protein and the development of diabetes in older adults.In this study, we examined the sex-specific association of plasma fetuin-A levels with prevalent and incident type 2 diabetes among community-dwelling older adults from the Rancho Bernardo Study. We used data from a baseline oral glucose tolerance test to examine the influence of glucose homeostasis as well as a number of other potential mediators and confounders on study findings. Based on the existing literature, we hypothesized that higher fetuin-A levels would be associated with dysglycemia and increased risk of diabetes in both older men and older women.     

Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study

OBJECTIVEIslet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.RESEARCH DESIGN AND METHODSWe used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.RESULTSThe hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76–3.63] and 2.48 [1.79–3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16–0.72] and 0.48 [0.24–0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70–6.72]) and an AP of 0.46 (0.12–0.80) compared with antibody-negative individuals with high n-3 PUFAs.CONCLUSIONSHigh fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.     

Ideal Cardiovascular Health and Incident Cardiovascular Disease Among Adults: A Systematic Review and Meta-analysis

Objective

To investigate the association between ideal cardiovascular health (CVH) metrics and incident cardiovascular disease (CVD) by conducting a systematic review and meta-analysis of prospective cohort studies.

Sulfonylurea Use and Incident Cardiovascular Disease Among Patients With Type 2 Diabetes: Prospective Cohort Study Among Women

OBJECTIVE

Evidence is inconsistent for the association between sulfonylurea use and risk of cardiovascular disease among patients with diabetes. We aimed to prospectively evaluate this association using the Nurses’ Health Study (NHS), a well-established cohort of U.S. women with long-term follow-up.

RESEARCH DESIGN AND METHODS

We followed 4,902 women (mean age 68 years) with diabetes (mean duration 11 years), but without cardiovascular disease at baseline. The use of sulfonylureas and other medications was self-reported at baseline and during the follow-up period of up to 10 years. Cox proportional hazards regression models were used to estimate the relative risk (RR) and 95% CI for the association between the sulfonylurea use and incident cardiovascular disease while accounting for potential confounders, including age, diabetes duration, diabetes-related complications, other antihyperglycemic medications, BMI, lifestyle factors, family history of cardiovascular diseases, and present chronic conditions. We also applied the propensity score stratification method to address the possibility of residual confounding.

RESULTS

We identified 339 incident cases of cardiovascular disease, including 191 cases of coronary heart disease (CHD) and 148 cases of stroke. A longer duration of sulfonylurea use was significantly associated with a higher risk of CHD (P for trend = 0.002); the RRs for CHD were 1.24 (95% CI 0.85–1.81) for patients who used sulfonylurea therapy for 1–5 years, 1.51 (0.94–2.42) for 6–10 years, and 2.15 (1.31–3.54) for >10 years, compared with nonusers. Compared with users of metformin monotherapy, the RR for CHD was 3.27 (1.31–8.17) for those who were treated with the combination of metformin and sulfonylurea. The analysis using propensity score stratification yielded similar results. We did not observe a significant association between sulfonylurea therapy and stroke risk.

CONCLUSIONS

Long-term use of sulfonylureas was associated with a significantly higher risk of developing CHD among women with diabetes.     

The Association Between Dietary Flavonoid and Lignan Intakes and Incident Type 2 Diabetes in European Populations: The EPIC-InterAct study

OBJECTIVE

To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations.

RESEARCH DESIGN AND METHODS

The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis.

RESULTS

In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77–1.04]; P valuetrend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72–1.07]; P valuetrend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69–0.95]; P valuetrend = 0.020) and flavanols (HR 0.82 [95% CI 0.68–0.99]; P valuetrend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57–0.93]; P valuetrend = 0.029), were associated with a significantly reduced hazard of diabetes.

CONCLUSIONS

Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.The prevalence of diabetes is markedly increasing worldwide, with the number of people with diabetes projected to rise from 366 million in 2011 to 552 million in 2030 (1). Dietary patterns characterized by higher consumption of fruit and vegetables (2), such as within a Mediterranean diet (3), are associated with a reduced risk of type 2 diabetes. Flavonoids and lignans are bioactive polyphenols that are contained in plant-based foods such as fruits, vegetables, nuts, legumes, cocoa, and cereals, and in beverages such as tea, wine, and juices (4), and have been proposed to have a potential role in the prevention of type 2 diabetes through diverse biological effects, including antioxidant and anti-inflammatory properties and insulin sensitivity–enhancing effects (5–7).Epidemiological evidence for an association between dietary intake of flavonoids and the risk of type 2 diabetes is inconsistent (8–13). For the six flavonoid subclasses, flavanols (including flavan-3-ol monomers, proanthocyanidins, and theaflavins), anthocyanidins, flavonols, flavanones, flavones, and isoflavones (Supplementary Table 1), a range of associations with diabetes has been reported in six prospective studies (8–13). An inverse significant association with type 2 diabetes was observed with anthocyanidins (15% risk reduction in a comparison of extreme quintiles), and significant inverse trends were observed with some flavonols (quercetin and myricetin) in a pooled analysis of Nurses’ Health Study I and II and the Health Professionals Follow-Up Study (8) and the Finnish Mobile Clinic Health Examination Survey (10), respectively. However, no associations were reported in the other two U.S.-based studies (Women’s Health Study and Iowa Women’s Health Study) (9,11) and for any other flavonoid subclasses (8–11). Among two Asian studies, the Singapore Chinese Health Study reported an inverse association of diabetes with soy intake and an inverse borderline significant association with isoflavone intake (12), whereas the Japan Public Health Centre-Based Prospective Study observed no significant association between soy or isoflavone intakes and type 2 diabetes in the whole population; however, among overweight Japanese women there was an inverse association (13). To our knowledge, there are no studies evaluating the association of dietary lignan intake with type 2 diabetes, although some experimental studies have shown promising antidiabetic properties (14,15).In light of the inconsistent current evidence, and in particular the paucity of information in European populations with considerable variability in flavonoid and lignan intakes, the aim of this study was to investigate the association between dietary flavonoid and lignan intakes, and the risk of developing type 2 diabetes in Europe. In particular, the use of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study, which was conducted across eight countries in Europe with substantial variation in the intake of flavonoids, enabled us to examine these associations comprehensively in a European population.     

Excessive Loss of Skeletal Muscle Mass in Older Adults With Type 2 Diabetes

OBJECTIVE

A loss of skeletal muscle mass is frequently observed in older adults. The aim of the study was to investigate the impact of type 2 diabetes on the changes in body composition, with particular interest in the skeletal muscle mass.

RESEARCH DESIGN AND METHODS

We examined total body composition with dual-energy X-ray absorptiometry annually for 6 years in 2,675 older adults. We also measured mid-thigh muscle cross-sectional area (CSA) with computed tomography in year 1 and year 6. At baseline, 75-g oral glucose challenge tests were performed. Diagnosed diabetes (n = 402, 15.0%) was identified by self-report or use of hypoglycemic agents. Undiagnosed diabetes (n = 226, 8.4%) was defined by fasting plasma glucose (≥7 mmol/l) or 2-h postchallenge plasma glucose (≥11.1 mmol/l). Longitudinal regression models were fit to examine the effect of diabetes on the changes in body composition variables.

RESULTS

Older adults with either diagnosed or undiagnosed type 2 diabetes showed excessive loss of appendicular lean mass and trunk fat mass compared with nondiabetic subjects. Thigh muscle CSA declined two times faster in older women with diabetes than their nondiabetic counterparts. These findings remained significant after adjusting for age, sex, race, clinic site, baseline BMI, weight change intention, and actual weight changes over time.

CONCLUSIONS

Type 2 diabetes is associated with excessive loss of skeletal muscle and trunk fat mass in community-dwelling older adults. Older women with type 2 diabetes are at especially high risk for loss of skeletal muscle mass.Age-related loss of skeletal muscle mass or sarcopenia results in decreased skeletal muscle strength, mobility limitations, physical disability, and eventually high mortality among the elderly (1–3). However, little is known about the causes or risk factors associated with loss of skeletal muscle mass in older adults. In addition, although weight gain and accumulation of abdominal fat have been known as strong risk factors for the development of type 2 diabetes (4), the changes in body composition after the onset of diabetes are not well documented. We have observed cross-sectionally that older adults with type 2 diabetes have an altered body composition and low skeletal muscle strength compared with nondiabetic older adults (5). We also reported that older adults with type 2 diabetes lost their knee extensor strength more rapidly than their nondiabetic counterparts (6).The effects of type 1 diabetes on protein metabolism seem to be clear, as insulin deprivation causes a profound increase in catabolism, especially in skeletal muscle (7,8). However, the effect of type 2 diabetes on protein metabolism is less clear, since the results of previous studies are inconsistent (9–12). Few studies have examined the effect of type 2 diabetes on the quantity of skeletal muscle mass in humans.In the Health, Aging, and Body Composition Study (Health ABC Study), we assessed the changes in total and regional lean and fat mass over 6 years with precise measures of body composition with dual-energy X-ray absorptiometry (DEXA) and computed tomography (CT). The aim of the study was to investigate the impact of type 2 diabetes on the changes in body composition, with particular interest on the skeletal muscle, in community-dwelling well-functioning older adults. We hypothesized that older adults with type 2 diabetes would show more loss of lean skeletal muscle mass than older adults without diabetes.     

Relations Between Subclinical Disease Markers and Type 2 Diabetes,Metabolic Syndrome,and Incident Cardiovascular Disease: The Jackson Heart Study

OBJECTIVE

The presence of subclinical disease measures has been directly associated with the development of cardiovascular disease (CVD) in whites. African Americans (AAs) in the U.S. are at higher risk of CVD compared with non-Hispanic whites; however, data on the prevalence of subclinical disease measures in AAs and their association to CVD remain unclear and may explain the higher CVD risk in this group.

RESEARCH DESIGN AND METHODS

We evaluated 4,416 participants attending the first examination of the Jackson Heart Study (mean age 54 years; 64% women) with available subclinical disease measures.

RESULTS

There were 1,155 participants (26%) with subclinical disease, defined as the presence of one or more of the following: peripheral arterial disease, left ventricular hypertrophy, microalbuminuria, high coronary artery calcium (CAC) score, and low left ventricular ejection fraction. In cross-sectional analyses using multivariable-adjusted logistic regression, participants with metabolic syndrome (MetS) or diabetes (DM) had higher odds of subclinical disease compared with those without MetS and DM (odds ratios 1.55 [95% CI 1.30–1.85] and 2.86 [95% CI 2.32–3.53], respectively). Furthermore, the presence of a high CAC score and left ventricular hypertrophy were directly associated with the incidence of CVD (265 events) in multivariable-adjusted Cox proportional hazards regression models (P < 0.05). In prospective analyses, having MetS or DM significantly increased the hazard of incident CVD, independent of the presence of subclinical disease (P < 0.001).

CONCLUSIONS

In our community-based sample of AAs, we observed a moderately high prevalence of subclinical disease, which in turn translated into a greater risk of CVD, especially in people with MetS and DM.     

Incidence of Remission in Adults With Type 2 Diabetes: The Diabetes & Aging Study

OBJECTIVETo estimate the incidence of remission in adults with type 2 diabetes not treated with bariatric surgery and to identify variables associated with remission.RESULTSThe incidence density (remissions per 1,000 person-years; 95% CI) of partial, complete, or prolonged remission was 2.8 (2.6–2.9), 0.24 (0.20–0.28), and 0.04 (0.01–0.06), respectively. The 7-year cumulative incidence of partial, complete, or prolonged remission was 1.47% (1.40–1.54%), 0.14% (0.12–0.16%), and 0.007% (0.003–0.020%), respectively. The 7-year cumulative incidence of achieving any remission was 1.60% in the whole cohort (1.53–1.68%) and 4.6% in the subgroup with new-onset diabetes (<2 years since diagnosis) (4.3–4.9%). After adjusting for demographic and clinical characteristics, correlates of remission included age >65 years, African American race, <2 years since diagnosis, baseline HbA_1c level <5.7% (<39 mmol/mol), and no diabetes medication at baseline.CONCLUSIONSIn community settings, remission of type 2 diabetes does occur without bariatric surgery, but it is very rare.     

Activity and Occupational Demands of Type Two Diabetes: The Voice of Mexican-American Older Adults

ABSTRACT

Type two diabetes mellitus has become a worldwide epidemic that directly or indirectly has impacted people everywhere. High incidence of diabetes in older adult Mexican-Americans poses serious, complex issues. Aim: The purpose of the study was to illuminate the cultural perspectives of highly motivated first-generation, bilingual Mexican-American older adults with T2DM, who accepted the activity and occupational demands and chose to follow the diabetes self-care regimen. Method: Emergent themes were extracted from focus groups using a phenomenological approach. Results: Themes were (1) “We had reasons”; (2) “Everyone had a different learning curve.”; (3) “Cultural issues made changing lifestyle difficult”; (4) and “Sharing helps us.” Conclusions: The inquiry revealed the shared perceptions and cultural nuances that may challenge Mexican-American people with diabetes, who try to adapt to lifestyle changes and occupational demands. Culturally-sensitive activity-based interventions that might facilitate self-care mastery were suggested. Future research is needed to facilitate OT reimbursement for self-care at the secondary prevention level.     

Food Intake Patterns Associated With Incident Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study

OBJECTIVE—Markers of hemostasis and inflammation such as plasminogen activator inhibitor-1 (PAI-1) and fibrinogen have been associated with risk of type 2 diabetes. We aimed to identify food intake patterns influencing this pathway and evaluate their association with incident diabetes.RESEARCH DESIGN AND METHODS—The Insulin Resistance Atherosclerosis Study cohort included 880 middle-aged adults initially free of diabetes. At the 5-year follow-up, 144 individuals had developed diabetes. Usual dietary intake was ascertained with a 114-item food frequency questionnaire. Using reduced rank regression, we identified a food pattern maximizing the explained variation in PAI-1 and fibrinogen. Subsequently, the food pattern–diabetes association was evaluated using logistic regression.RESULTS—High intake of the food groups red meat, low-fiber bread and cereal, dried beans, fried potatoes, tomato vegetables, eggs, cheese, and cottage cheese and low intake of wine characterized the pattern, which was positively associated with both biomarkers. With increasing pattern score, the odds of diabetes increased significantly (P_trend < 0.01). After multivariate adjustment, the odds ratio comparing extreme quartiles was 4.3 (95% CI 1.7–10.8). Adjustment for insulin sensitivity and secretion and other metabolic factors had little impact (4.9, 1.8–13.7).CONCLUSIONS—Our findings provide support for potential behavioral prevention strategies, as we identified a food intake pattern that was strongly related to PAI-1 and fibrinogen and independently predicted type 2 diabetes.Markers of hemostasis and inflammation are considered risk factors in the pathogenesis of type 2 diabetes (1,2). Data from the Insulin Resistance Atherosclerosis Study (IRAS) indicate that the effect of plasminogen activator inhibitor-1 (PAI-1) on diabetes risk is independent not only of adiposity but also of insulin sensitivity (1). In the context of diabetes prevention, these findings challenge us to explore the determinants of the prothrombotic and inflammatory state, particularly modifiable risk factors such as dietary intake.The importance of food and nutrient intake in the development of diabetes and its precursors is well recognized (3). The Diabetes Prevention Program trial provides evidence for the effectiveness of dietary and lifestyle modification approaches in the prevention of type 2 diabetes among high-risk individuals (4). The focus of the lifestyle intervention in the Diabetes Prevention Program was weight loss via modification of energy and fat intake and physical activity. To date, very few intervention trials have evaluated the impact of larger dietary patterns on health outcomes (5–7).Two general approaches have dominated the field of observational research on dietary patterns: the a priori approach uses prior knowledge such as dietary recommendations to create quality indexes (8); and the exploratory approaches such as principal components, factor analysis, or cluster analysis are entirely empirical, data-driven methods. Recently, reduced rank regression (RRR) has been introduced as a method that combines the strengths of both approaches (9) because it identifies patterns among food groups by concurrently using data on a set of response variables (ideally biomarkers) selected because of known associations with the disease of interest. Two recent studies using RRR have revealed strong associations between food intake patterns and risk of diabetes (10,11). We aimed to identify RRR-determined food intake patterns that affect diabetes-related inflammatory biomarkers and to evaluate their association with incident type 2 diabetes, taking into account measures of insulin sensitivity and secretion in the IRAS population.     

Depressive Symptoms and Risk of Type 2 Diabetes in a National Sample of Middle-Aged and Older Adults: The English Longitudinal Study of Aging

OBJECTIVE

To examine the association between baseline elevated depressive symptoms and incident type 2 diabetes in a national sample of people aged ≥50 years.

RESEARCH DESIGN AND METHODS

The sample consisted of 6,111 individuals free from self-reported doctor-diagnosed diabetes at baseline in 2002–2003. The eight-item Center for Epidemiological Studies–Depression (CES-D) scale was the measurement of depressive symptoms. Cox proportional hazards regression models were used to assess whether baseline elevated (≥4) depressive symptoms were associated with a higher risk of type 2 diabetes over 45.8 months of follow-up.

RESULTS

The hazard ratio (HR) for diabetes was 1.62 (95% CI 1.15–2.29) in a model adjusted for age, sex, marital status, education, total net household wealth, cardiovascular and psychiatric and other noncardiovascular comorbidities, BMI, and health behaviors for participants with elevated CES-D symptoms compared with those without. Complementary analysis performed for a subsample (n = 5,090) showed that additional adjustment of this model for use of antidepressants did not explain the association (HR 1.58, 95% CI 1.09–2.29).

CONCLUSIONS

Elevated depressive symptoms were associated with a higher risk of developing type 2 diabetes after accounting for sociodemographic, lifestyle, and clinical factors in a national sample of people aged ≥50 years.Depression is a known comorbid condition of diabetes. Individuals with diabetes have increased odds of being depressed and consistently higher prevalence rates of depression than their counterparts without diabetes (1). An accumulating body of research shows that type 2 diabetes is a risk factor for recurrent depression (2), but longitudinal studies also suggest that depression and elevated depressive symptoms are related to subsequent incidence of diabetes (3–10). Two recent meta-analyses of longitudinal studies suggest that depression is associated with a 40–60% increased risk of developing type 2 diabetes (11,12). The etiology and pathogenic mechanism of this association is poorly understood. It has been suggested that unhealthy behaviors (i.e., physical inactivity and smoking), obesity, and use of psychotropic medication may be parts of the causal pathway linking depression to type 2 diabetes (3,11,13).The majority of previous longitudinal studies on the association between depressive symptoms and incident diabetes have not accounted adequately for socioeconomic status (SES), and therefore their results might be biased because of residual confounding. They have also generally failed to account for baseline comorbidities such as cardiovascular, noncardiovascular, and psychiatric diseases, which might explain the association between depression and diabetes. Moreover, more research is needed on the use of antidepressants and other psychotropic medication as a depression-related risk factor for diabetes in older samples, since evidence on this issue is conflicting (6,8,9,14).We used data from the English Longitudinal Study of Aging (ELSA), a national prospective cohort study of community-dwelling middle-aged and older men and women, to examine whether baseline elevated depressive symptoms measured by the Center for Epidemiological Studies–Depression (CES-D) scale were associated with a higher risk of developing type 2 diabetes. We adjusted for a wide range of potential confounders including education and wealth as markers of SES and baseline comorbidities including psychiatric diseases. We then explored whether health behaviors, BMI, and use of antidepressants or other psychotropic medication mediated the association between elevated baseline depressive symptoms and incident type 2 diabetes.     

Clinical and Subclinical Macrovascular Disease as Predictors of Cognitive Decline in Older Patients With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study

OBJECTIVE

Macrovascular disease may contribute to increased risk of accelerated cognitive decline in patients with type 2 diabetes. We aimed to determine associations of measures of macrovascular disease with cognitive change in a cognitively healthy older population with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Eight hundred thirty-one men and women (aged 60–75 years) attended two waves of the prospective Edinburgh Type 2 Diabetes Study (ET2DS). At baseline, clinical and subclinical macrovascular disease was measured, including cardiovascular event history, carotid intima-media thickness (cIMT), ankle brachial index (ABI), and serum N-terminal probrain natriuretic peptide (NT-proBNP). Seven neuropsychological tests were administered at baseline and after 4 years; scores were combined to a standardized general ability factor (g). Adjustment of follow-up g for baseline g assessed 4-year cognitive change. Adjustment for vocabulary (estimated premorbid ability) was used to estimate lifetime cognitive change.

RESULTS

Measures of cognitive decline were significantly associated with stroke, NT-proBNP, ABI, and cIMT, but not with nonstroke vascular events. The association of stroke with increased estimated lifetime cognitive decline (standardized β, −0.12) and of subclinical markers with actual 4-year decline (standardized β, −0.12, 0.12, and −0.15 for NT-proBNP, ABI, and cIMT, respectively) reached the Bonferroni-adjusted level of statistical significance (P < 0.006). Results altered only slightly on adjustment for vascular risk factors.

CONCLUSIONS

Stroke and subclinical markers of cardiac stress and generalized atherosclerosis are associated with cognitive decline in older patients with type 2 diabetes. Further investigation into the potential use of subclinical vascular disease markers in predicting cognitive decline is warranted.Cognitive abilities are essential for independent living in later life, and some domains of cognitive functioning decline in mean level from relatively early adulthood (1). Age-related cognitive decline is accompanied by pathological changes in the brain, including cerebral microvascular changes, and although individual differences exist in the severity of age-related microvascular damage in the brain, this is difficult to investigate noninvasively. Systemic atherosclerotic changes in the body may serve as a marker of vascular-related changes in the brain (2) that, in turn, lead to cognitive deficits (3,4). However, the potential of large vessel changes distant from the brain itself to function as markers of cognitive decline remains unclear. We aimed to study a range of measures of clinical and subclinical macrovascular disease that focus on different areas of the vasculature or different underlying pathophysiological mechanisms to assess which of these might function as proxies of cognitive decline.Understanding the role of macrovascular disease in age-related cognitive impairment is particularly important in diabetes, given the higher prevalence of atherosclerotic large vessel disease as well as the accelerated cognitive decline and increased risk of cognitive impairment (5,6) associated with this condition, and the potentially modifiable nature of macrovascular disease (7). The prevalence of stroke, of transient ischemic attack (TIA) (8), and of coronary heart disease (9) are higher in diabetic populations than in nondiabetic populations, and average natriuretic peptide levels, a marker of cardiac stress, are increased (10). Markers of subclinical atherosclerosis also are altered, with increased average carotid intima-media thickness (cIMT) (11) and reduced mean ankle brachial index (ABI) (12). Despite this, investigation into the role of macrovascular disease in age-related cognitive impairment in people with diabetes is limited compared with investigation into this issue in the general (predominantly nondiabetic) population. We set out to determine the association of a variety of measures of subclinical macrovascular disease and cardiovascular event categories with cognitive decline in a sample of older people, all of whom had diabetes (the Edinburgh Type 2 Diabetes Study [ET2DS]). We did so using two cognitive outcomes, actual late-life cognitive change over a 4-year period and estimated lifetime cognitive change. These analyses are timely given the increasing prevalence of diabetes at younger ages (13) that, together with greater survival (14) and greater lifetime exposure to diabetes in current generations, is likely to contribute to increasing prevalence of cognitive impairment.     

Lipoprotein Particles and Incident Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis

OBJECTIVE

In the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated associations of baseline levels of a lipoprotein-based insulin resistance (IR) index (LP-IR), IR-related lipoprotein particles, mean particle sizes, and lipids, with incident type 2 diabetes, independent of confounders, glucose, insulin, and HOMA-IR.

RESEARCH DESIGN AND METHODS

Among 5,314 adults aged 45–84 years without baseline diabetes or cardiovascular disease, 656 cases of diabetes were identified during a mean follow-up of 7.7 years. Lipoprotein particle concentrations, size, and LP-IR were determined by nuclear magnetic resonance spectroscopy of stored baseline plasma. Potential effect modification, by race/ethnicity, sex, baseline use of lipid-lowering medications or hormone therapy, or glucose strata (<90, 90–99, and ≥100 mg/dL), was also evaluated.

RESULTS

Higher levels of LP-IR, large VLDL particles (VLDL-P), small LDL particles, triglycerides (TG), and TG–to–HDL cholesterol (HDL-C) ratio and lower levels of large HDL particles, smaller HDL and LDL size, and larger VLDL size were significantly associated with incident diabetes adjusted for confounders and glucose or insulin. These also were similar by race/ethnicity, sex, and treatment group. Associations were similar for LP-IR, large VLDL-P, mean VLDL size, TG, and TG–to–HDL-C ratio; they persisted for LP-IR, large VLDL-P, or mean VLDL size adjusted for HOMA-IR or TG–to–HDL-C ratio and glucose but not for the TG–to–HDL-C ratio adjusted for LP-IR or for HOMA-IR or insulin if adjusted for LP-IR and glucose.

CONCLUSIONS

Among ethnically diverse men and women, LP-IR, large VLDL-P, large VLDL size, TG, and TG–to–HDL-C ratio were associated with incident diabetes independent of established risk factors, glucose, insulin, or HOMA-IR, as well as the use of lipid-lowering medications or hormone therapy.     

Cognitive Function in Adolescents and Young Adults With Youth-Onset Type 1 Versus Type 2 Diabetes: The SEARCH for Diabetes in Youth Study

OBJECTIVEPoor cognition has been observed in children and adolescents with youth-onset type 1 (T1D) and type 2 diabetes (T2D) compared with control subjects without diabetes. Differences in cognition between youth-onset T1D and T2D, however, are not known. Thus, using data from SEARCH for Diabetes in Youth, a multicenter, observational cohort study, we tested the association between diabetes type and cognitive function in adolescents and young adults with T1D (n = 1,095) or T2D (n = 285).RESEARCH DESIGN AND METHODSCognition was assessed via the National Institutes of Health Toolbox Cognition Battery, and age-corrected composite Fluid Cognition scores were used as the primary outcome. Confounder-adjusted linear regression models were run. Model 1 included diabetes type and clinical site. Model 2 additionally included sex, race/ethnicity, waist-to-height ratio, diabetes duration, depressive symptoms, glycemic control, any hypoglycemic episode in the past year, parental education, and household income. Model 3 additionally included the Picture Vocabulary score, a measure of receptive language and crystallized cognition.RESULTSHaving T2D was significantly associated with lower fluid cognitive scores before adjustment for confounders (model 1; P < 0.001). This association was attenuated to nonsignificance with the addition of a priori confounders (model 2; P = 0.06) and Picture Vocabulary scores (model 3; P = 0.49). Receptive language, waist-to-height ratio, and depressive symptoms remained significant in the final model (P < 0.01 for all, respectively).CONCLUSIONSThese data suggest that while youth with T2D have worse fluid cognition than youth with T1D, these differences are accounted for by differences in crystallized cognition (receptive language), central adiposity, and mental health. These potentially modifiable factors are also independently associated with fluid cognitive health, regardless of diabetes type. Future studies of cognitive health in people with youth-onset diabetes should focus on investigating these significant factors.