Non-invasive in vivo measurements of metabolic alterations in the type 2 diabetic brain by 1 H magnetic resonance spectroscopy.

Type 2 diabetes (T2D) is a complex chronic metabolic disorder characterized by hyperglycemia because of insulin resistance. Diabetes with chronic hyperglycemia may alter brain metabolism, including brain glucose and neurotransmitter levels; however, detailed, longitudinal studies of metabolic alterations in T2D are lacking. To shed insight, here, we characterized the consequences of poorly controlled hyperglycemia on neurochemical profiles that reflect metabolic alterations of the brain in both humans and animal models of T2D. Using in vivo 1 H magnetic resonance spectroscopy, we quantified 12 metabolites cross-sectionally in T2D patients and 20 metabolites longitudinally in T2D db/db mice versus db+ controls. We found significantly elevated brain glucose (91%, p < 0.001), taurine (22%, p = 0.02), glucose+taurine (56%, p < 0.001), myo-inositol (12%, p = 0.02), and choline-containing compounds (10%, p = 0.01) in T2D patients versus age- and sex-matched controls, findings consistent with measures in T2D db/db versus control db+ littermates. In mice, hippocampal and striatal neurochemical alterations in brain glucose, ascorbate, creatine, phosphocreatine, γ-aminobutyric acid, glutamate, glutamine, glutathione, glycerophosphoryl-choline, lactate, myo-inositol, and taurine persisted in db/db mice with chronic disease progression from 16 to 48 weeks of age, which were distinct from control db+ mice. Overall, our study demonstrates the utility of 1 H magnetic resonance spectroscopy as a non-invasive tool for characterizing and monitoring brain metabolic changes with T2D progression.

A dyadic multiple mediation model of patient and spouse stressors predicting patient dietary and exercise adherence via depression symptoms and diabetes self-efficacy.

Using dyadic data from 117 married couples in which one partner was diagnosed with Type 2 diabetes, the purpose of this study was to determine whether a number of specific patient and spouse stressors (chronic life stress, diabetes-specific stress, and physical health stress in the form of the number of comorbidities) were associated with Type 2 diabetes patients' dietary and exercise adherence through two potentially modifiable patient and spouse factors-depression symptoms and diabetes self-efficacy. We found that patient and spouse stressors, particularly patient and spouse diabetes stress and the number of patient comorbidities, were related to patient dietary and exercise adherence through patient depression symptoms and both patient and spouse diabetes self-efficacy. These conclusions were strengthened by incorporating a number of relevant control variables in our models and by testing four alternative models which supported our proposed model. These results are important because they provide further evidence of the significant role spouses' play in managing diabetes and they provide diabetes educators and clinicians with specific targets for intervention programming.

Long-term liraglutide treatment is associated with increased insulin content and secretion in ß-cells, and a loss of α-cells in ZDF rats.

The ultimate treatment goal of diabetes is to preserve and restore islet cell function. Treatment of certain diabetic animal models with incretins has been reported to preserve and possibly enhance islet function and promote islet cell growth. The studies reported here detail islet cell anatomy in animals chronically treated with the incretin analog, liraglutide. Our aim was to quantitatively and qualitatively analyze islet cells from diabetic animals treated with vehicle (control) or liraglutide to determine whether normal islet cell anatomy is maintained or enhanced with pharmaceutical treatment. We harvested pancreata from liraglutide and vehicle-treated Zucker Diabetic Fatty (ZDF) rats to examine islet structure and function and obtain isolated islets. Twelve-week-old male rats were assigned to 3 groups: (1) liraglutide-treated diabetic, (2) vehicle-treated diabetic, and (3) lean non-diabetic. Liraglutide was given SC twice daily for 9 weeks. As expected, liraglutide treatment reduced body weight by 15% compared to the vehicle-treated animals, eventually to levels that were not different from lean controls. At the termination of the study, blood glucose was significantly less in the liraglutide-treated rats compared to vehicle treated controls (485.8±22.5 and 547.2±33.1mg/dl, respectively). Insulin content/islet (measured by immunohistochemistry) was 34.2±0.7 pixel units in vehicle-treated rats, and 54.9±0.6 in the liraglutide-treated animals. Glucose-stimulated insulin secretion from isolated islets (measured as the stimulation index) was maintained in the liraglutide-treated rats, but not in the vehicle-treated. However, liraglutide did not preserve normal islet architecture. There was a decrease in the glucagon-positive area/islet and in the α-cell numbers/area with liraglutide treatment (6.5 cells/field), compared to vehicle (17.9 cells/field). There was an increase in ß-cell numbers, the ß- to α-cell ratio that was statistically higher in the liraglutide-treated rats (24.3±4.4) compared to vehicle (9.1±2.8). Disrupted mitochondria were more commonly observed in the α-cells (51.9±10.3% of cells) than in the ß-cells (27.2±4.4%) in the liraglutide-treated group. While liraglutide enhanced or maintained growth and function of certain islet cells, the overall ratio of α- to ß-cells was decreased and there was an absolute reduction in islet α-cell content. There was selective disruption of intracellular α-cell organelles, representing an uncoupling of the bihormonal islet signaling that is required for normal metabolic regulation. The relevance of the findings to long-term liraglutide treatment in people with diabetes is unknown and should be investigated in appropriately designed clinical studies.

Electronic Monitoring of Mom's Schedule (eMOMSTM): A Qualitative Study of Experiences in a Lifestyle Change Program with Lactation Support.

PURPOSE: To elicit feedback from participants who completed the eMOMSTM study, a feasibility randomized controlled trial (NCT04021602), on their perceptions of program strengths and weaknesses. STUDY DESIGN: Qualitative - Semi-structured, telephone interview guide using open-ended questions. SETTING: Rural Great Plains state, United States. PARTICIPANTS: Of 26 individuals who completed the eMOMSTM study, 24 consented to an interview. METHOD: Interviews were completed between October 2020 and May 2021. Audio-recordings were transcribed verbatim and organized in Microsoft 365. Data were analyzed using an exploratory, inductive thematic analysis. RESULTS: Participants' mean age was 27.5 (± 5.4) years and mean pre-pregnancy BMI was 29.5 kg/m2 (± 2.7). The majority (71%) were non-Hispanic White and 54% had a high school education/some college. Based on specific areas of inquiry, the following themes emerged: convenience of online program access using Facebook, importance of health coach's support and online interaction, positivity toward improving one's health, increased consciousness of health behaviors, diverse lactation educational needs, importance of educational materials on depression, and grief over the loss of birth expectations during COVID-19. CONCLUSION: Findings suggest participants' perceived value of a lifestyle change program coupled with lactation education and support delivered using social media. Findings inform future studies to further adapt lifestyle change programs.

Longitudinal Risk Prediction of Chronic Kidney Disease in Diabetic Patients Using a Temporal-Enhanced Gradient Boosting Machine: Retrospective Cohort Study.

BACKGROUND: Artificial intelligence-enabled electronic health record (EHR) analysis can revolutionize medical practice from the diagnosis and prediction of complex diseases to making recommendations in patient care, especially for chronic conditions such as chronic kidney disease (CKD), which is one of the most frequent complications in patients with diabetes and is associated with substantial morbidity and mortality. OBJECTIVE: The longitudinal prediction of health outcomes requires effective representation of temporal data in the EHR. In this study, we proposed a novel temporal-enhanced gradient boosting machine (GBM) model that dynamically updates and ensembles learners based on new events in patient timelines to improve the prediction accuracy of CKD among patients with diabetes. METHODS: Using a broad spectrum of deidentified EHR data on a retrospective cohort of 14,039 adult patients with type 2 diabetes and GBM as the base learner, we validated our proposed Landmark-Boosting model against three state-of-the-art temporal models for rolling predictions of 1-year CKD risk. RESULTS: The proposed model uniformly outperformed other models, achieving an area under receiver operating curve of 0.83 (95% CI 0.76-0.85), 0.78 (95% CI 0.75-0.82), and 0.82 (95% CI 0.78-0.86) in predicting CKD risk with automatic accumulation of new data in later years (years 2, 3, and 4 since diabetes mellitus onset, respectively). The Landmark-Boosting model also maintained the best calibration across moderate- and high-risk groups and over time. The experimental results demonstrated that the proposed temporal model can not only accurately predict 1-year CKD risk but also improve performance over time with additionally accumulated data, which is essential for clinical use to improve renal management of patients with diabetes. CONCLUSIONS: Incorporation of temporal information in EHR data can significantly improve predictive model performance and will particularly benefit patients who follow-up with their physicians as recommended.

Robust clinical marker identification for diabetic kidney disease with ensemble feature selection.

Objective: Diabetic kidney disease (DKD) is one of the most frequent complications in diabetes associated with substantial morbidity and mortality. To accelerate DKD risk factor discovery, we present an ensemble feature selection approach to identify a robust set of discriminant factors using electronic medical records (EMRs). Material and Methods: We identified a retrospective cohort of 15 645 adult patients with type 2 diabetes, excluding those with pre-existing kidney disease, and utilized all available clinical data types in modeling. We compared 3 machine-learning-based embedded feature selection methods in conjunction with 6 feature ensemble techniques for selecting top-ranked features in terms of robustness to data perturbations and predictability for DKD onset. Results: The gradient boosting machine (GBM) with weighted mean rank feature ensemble technique achieved the best performance with an AUC of 0.82 [95%-CI, 0.81-0.83] on internal validation and 0.71 [95%-CI, 0.68-0.73] on external temporal validation. The ensemble model identified a set of 440 features from 84 872 unique clinical features that are both predicative of DKD onset and robust against data perturbations, including 191 labs, 51 visit details (mainly vital signs), 39 medications, 34 orders, 30 diagnoses, and 95 other clinical features. Discussion: Many of the top-ranked features have not been included in the state-of-art DKD prediction models, but their relationships with kidney function have been suggested in existing literature. Conclusion: Our ensemble feature selection framework provides an option for identifying a robust and parsimonious feature set unbiasedly from EMR data, which effectively aids in knowledge discovery for DKD risk factors.

Evaluative coping, emotional distress, and adherence in couples with Type 2 diabetes.

INTRODUCTION: Spousal support is one of the strongest and most consistent predictors of Type 2 diabetes treatment adherence. However, the effects of both spouses' evaluations of dyadic coping on emotional distress and patients' physical health remain largely unknown. METHOD: Dyadic data from 117 married couples in which one member is diagnosed with Type 2 diabetes were evaluated in two separate models to explore the associations between (a) patients' and spouses' depression symptoms and patients' adherence to dietary and exercise regimens, and (b) patients' and spouses' acute stress levels and patients' adherence to dietary and exercise regimens. Finally, evaluative dyadic coping was included as a possible moderator between these associations. RESULTS: Results from an actor-partner interdependence model revealed significant actor effects of patients' depression symptoms on patients' adherence to dietary and exercise regimens. Spouses' evaluation of dyadic coping attenuated the direct paths between spouses' depression symptoms and patients' adherence to dietary regimens. No direct pathways were found from patients' or spouses' acute stress to patients' adherence to dietary and exercise regimens. However, spouses' evaluation of dyadic coping attenuated the direct paths between spouses' acute stress and patients' adherence to dietary regimens. DISCUSSION: Tapping into spouses' evaluations of dyadic coping has significant implications for patients' diabetes health outcomes (e.g., adherence to dietary and exercise treatment regimens). Findings from this study highlight the need for systemic interventions targeting both partners. (PsycINFO Database Record

Baseline Characteristics of the Vitamin D and Type 2 Diabetes (D2d) Study: A Contemporary Prediabetes Cohort That Will Inform Diabetes Prevention Efforts.

OBJECTIVE: To describe baseline characteristics of the Vitamin D and Type 2 Diabetes (D2d) study, the first large U.S. diabetes prevention clinical trial to apply current American Diabetes Association (ADA) criteria for prediabetes. RESEARCH DESIGN AND METHODS: This is a multicenter (n = 22 sites), randomized, double-blind, placebo-controlled, primary prevention clinical trial testing effects of oral daily 4,000 IU cholecalciferol (D3) compared with placebo on incident diabetes in U.S. adults at risk for diabetes. Eligible participants were at risk for diabetes, defined as not meeting criteria for diabetes but meeting at least two 2010 ADA glycemic criteria for prediabetes: fasting plasma glucose (FPG) 100-125 mg/dL, 2-h postload glucose (2hPG) after a 75-g oral glucose load 140-199 mg/dL, and/or a hemoglobin A1c (HbA1c) 5.7-6.4% (39-46 mmol/mol). RESULTS: A total of 2,423 participants (45% of whom were women and 33% nonwhite) were randomized to cholecalciferol or placebo. Mean (SD) age was 59 (9.9) years and BMI 32 (4.5) kg/m2. Thirty-five percent met all three prediabetes criteria, 49% met the FPG/HbA1c criteria only, 9.5% met the 2hPG/FPG criteria only, and 6.3% met the 2hPG/HbA1c criteria only. Black participants had the highest mean HbA1c and lowest FPG concentration compared with white, Asian, and other races (P < 0.01); 2hPG concentration did not differ among racial groups. When compared with previous prediabetes cohorts, the D2d cohort had lower mean 2hPG concentration but similar HbA1c and FPG concentrations. CONCLUSIONS: D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria.

Mealtime 50/50 basal + prandial insulin analogue mixture with a basal insulin analogue, both plus metformin, in the achievement of target HbA1c and pre- and postprandial blood glucose levels in patients with type 2 diabetes: a multinational, 24-week, randomized, open-label, parallel-group comparison.

BACKGROUND: In people without diabetes, approximately 50% of daily insulin secretion is basal and the remainder is postprandial. Hence, it would be expected that insulin replacement therapy in a 50/50 ratio with each meal would mimic physiologic insulin secretion better than treatment with once-daily basal insulin in patients with diabetes mellitus. Using lispro mix (LM) 50/50 before meals may be a logical approach to achieving glycemic targets (glycosylated hemoglobin [HbA(lc)] and pre- and postprandial blood glucose [BG] concentrations) in these patients. OBJECTIVE: The aim of this study was to test the hypothesis that treatment with a premixed insulin analogue containing 50/50 basal + prandial insulins administered before each meal would achieve lower overall and mealtime glycemic control than once-daily basal insulin analogue, both plus metformin (Met), in patients with type 2 diabetes mellitus. METHODS: This 24-week, randomized, open-label, parallel-group trial was conducted at 38 sites across Australia, Greece, India, The Netherlands, Poland, Puerto Rico, and the United States. Male and female patients aged 35 to 75 years with type 2 diabetes mellitus and an HbA(1c) level of 6.5% to 11.0%, who were receiving metformin and/or a sulfonylurea with a stable dose of 0 to 2 daily insulin injections over the previous 3 months were eligible. Patients were randomly assigned to receive LM50/50 (50% insulin lispro protamine suspension [ILPS] and 50% lispro) TID plus metformin (to a maximally tolerated daily dosage of 500-1000 mg BID) (LM50/50 + Met) or insulin glargine QD at bedtime plus metformin (500-1000 mg BID) (G + Met) for 24 weeks. With LM50/50 + Met, the insulin dose was titrated to target a fasting BG (FBG) level of <6.7 mmol/L (<120 mg/dL) and a 2-hour post-prandial BG (PPBG) level of <8.0 mmol/L (<144 mg/dL); those who did not reach the FBG target would be switched from presupper LM50/50 to LM75/25 (75% ILPS, 25% lispro). RESULTS: A total of 315 patients were randomized and received treatment (158 women, 157 men; mean age, 57.7 years; mean body mass index, 32.1 kg/m2; LM50/50 + Met, 157 patients; G + Met, 158 patients). At 24 weeks, the mean (SD)HbA(1c) level was significantly lower in the LM50/50 + Met group than in the G + Met group (7.1% [0.9%] vs 7.5% [1.0%]; P<0.001), and the proportion who reached an HbA(1c) target of < or = 7.0% was greater (88 [56.1%] vs 63 [39.9%]; P = 0.005). The G + Met group had a lower mean (SD)FBG value (6.5 [1.6] vs 8.1 [1.8] mmol/L; P<0.001). The LM50/50 + Met group had lower mean preprandial BG levels prelunch (7.4 [1.9] vs 7.9 [2.1] mmol/L; P=0.03) and presupper (8.3 [2.0] vs 8.9 [2.8] mmol/L; P=0.04). The LM50/50 + Met group also had lower mean 2-hour PPBG values postbreakfast (8.7 [2.2] vs 9.2 [2.5] mmol/L; P=0.03), postlunch (8.4 [1.9] vs 9.8 [2.6], mmol/L; p<0.001), and postsupper (8.7 [2.2] vs 10.7 [3.2], mmol/L; P<0.001). The mean (SD) total insulin doses at study end point were 0.7 (0.3) U/kg in the LM50/50 + Met group and 0.6 (0.3) U/kg in the G + Met group (P<0.001). The mean (SD)M-value (an expression of mean glycemia and the effect of glucose swings) was statistically similar between the 2 groups at baseline but significantly lower in the LM50/50 + Met group at end point (17.3 [13.8] vs 25.1 [24.8] mmol/L; P<0.001). During the entire treatment period, mean (SD) overall and nocturnal hypoglycemia rates (episodes per patient for 30 days) were statistically similar between the 2 groups (overall, 0.8 [1.4] vs 0.5 [1.0]; nocturnal, 0.2 [0.7] vs 0.3 [0.6]). At end point, the mean (SD) nocturnal hypoglycemia rates were similar between the 2 groups (0.2 [0.9] vs 0.2 [0.6]), but the overall and non-nocturnal hypoglycemia rates were higher with LM50/50 + Met (overall, 0.7 [1.7] vs 0.3 [0.8]; P=0.02; non-nocturnal, 0.5 [1.2] vs 0.1 [0.4]; P=0.002). CONCLUSION: In these patients with type 2 diabetes, mealtime LM50/50 + Met was associated with lower overall (HbA(1c)) and preprandial BG and PPBG levels (except for FBG), with similar nocturnal hypoglycemia and less glycemic variability, compared with G + Met.

Associations Between Economic Pressure and Diabetes Efficacy in Couples With Type 2 Diabetes.

Objective: The purpose of this study was to explore dyadic associations between economic pressure and diabetes self-efficacy via emotional distress in patients with type 2 diabetes and their partners. Background: Understanding how economic pressure is associated with successful diabetes management is an important area for research, as couples with type 2 diabetes can incur heavy economic pressures that could likely influence diabetes outcomes. Method: Data from 117 married couples were used to test actor-partner associations using moderated mediation analyses in a structural equation modeling framework. Problem-solving communication was tested as a possible moderator of the economic pressure-emotional distress pathway. Results: Results revealed that greater patient economic pressure was associated with lower patient and spouse confidence in the patient's diabetes management ability through higher levels of patient emotional distress. The deleterious association between economic pressure and emotional distress was less pronounced when spouses reported more effective problem-solving communication. Conclusion: These results provide evidence that the economic pressure couples with type 2 diabetes face may reduce the patient and spouse's confidence in the patient's diabetes management ability. Implications: This study demonstrates the importance of couple's relationship processes in buffering the impact of economic pressure on diabetes management, providing a clear target for intervention and education efforts.

Does Personality Matter in Diabetes Adherence? Exploring the Pathways between Neuroticism and Patient Adherence in Couples with Type 2 Diabetes.

BACKGROUND: Personality has received some attention in the Type 2 diabetes literature; however, research has not linked personality and diabetes adherence behaviors (diet and exercise), identified pathways through which they are associated, nor taken into consideration important contextual factors that influence behavior (the patient's partner). METHODS: Dyadic data from 117 married, heterosexual couples in which one member is diagnosed with Type 2 diabetes was used to explore associations between each partner's neuroticism and patient dietary and exercise adherence through the pathways of negative affect, depression symptoms, and couple-level diabetes efficacy (both patient and spouse report of confidence in the patient's ability to adhere to diabetes management regimens). RESULTS: Results revealed that higher levels of neuroticism were associated with lower patient dietary and exercise adherence through (1) higher levels of depression symptoms (for patients' neuroticism) and negative affect (for spouses' neuroticism), and (2) lower levels of couple-level diabetes efficacy. CONCLUSIONS: The results from this study provide evidence that both patient and spouse personality traits are associated with patient dietary and exercise adherence through increased emotional distress-albeit different emotional pathways for patients and spouses-and lower couple confidence in the patients' ability to manage their diabetes.

Association of albuminuria with systolic and diastolic left ventricular dysfunction in type 2 diabetes: the Strong Heart Study.

OBJECTIVES: We sought to compare systolic and diastolic function in American Indians with diabetes mellitus (DM) based on albuminuria status. BACKGROUND: Albuminuria has been shown to predict cardiovascular disease (CVD) in populations with DM. However, the mechanism of the association of albuminuria and CVD is unclear. METHODS: We compared echo-derived indices of left ventricular (LV) systolic and diastolic function in three groups of American Indians with DM based on albuminuria status: I = no albuminuria (<30 mg albumin/g creatinine); II = microalbuminuria (30 to 300 mg/g); and III = macroalbuminuria (>300 mg/g). RESULTS: Group II and III were slightly older than Group I with no significant gender difference between groups. Systolic blood pressure increased and body mass index decreased from Group I to Group III. Left ventricular systolic function was lower in the groups with albuminuria with step-wise decreases in ejection fraction and stress-corrected midwall shortening (MWS) from Group I to Group III. Similar findings were noted in diastolic LV filling with lower mitral E/A ratios and longer deceleration times in groups with albuminuria. The proportion of participants with abnormal MWS and abnormal LV diastolic relaxation showed step-wise increases from no albuminuria to macroalbuminuria. In multivariate analysis, albuminuria status remained independently associated with both systolic and diastolic dysfunction after adjusting for age, gender, body mass index, systolic blood pressure, duration of diabetes, coronary artery disease, and LV mass. CONCLUSIONS: Albuminuria is independently associated with LV systolic and diastolic dysfunction in type 2 DM; this may explain in part the relationship of albuminuria to increased cardiovascular (CV) events in the DM population. Screening for albuminuria identifies individuals with high CV risk and possible cardiac dysfunction.

Hyperglycemia and its effect after acute myocardial infarction on cardiovascular outcomes in patients with Type 2 diabetes mellitus (HEART2D) Study design.

OBJECTIVE: Cardiovascular (CV) disease is the major cause of death in patients with diabetes. Up to 40% of patients with Type 2 diabetes mellitus (T2DM) who survive an initial myocardial infarction (MI) suffer a recurrent event within 2 years, the majority of which are fatal. One independent risk factor for cardiovascular disease (CVD) may be postprandial blood glucose (PPBG) excursions. The HEART2D study seeks to determine the effect that PPBG control has on cardiovascular outcomes in patients who suffered an MI within the 21 days before study enrollment. RESEARCH DESIGN AND METHODS: Approximately 1355 patients with T2DM with recent MI will be entered in this multicenter study of about 3.0-year duration. Using infarct severity and peri-infarct treatment as randomization factors, patients will be assigned to one of two insulin treatment strategies: (1) postprandial strategy: premeal insulin lispro with basal insulin at bedtime if needed (NPH insulin), targeting 2-h PPBG < or = 7.5 mmol/l or (2) basal strategy: insulin (NPH insulin twice daily or insulin glargine once daily; or premixed human insulin (70% NPH/30% regular; 30/70) twice daily), targeting fasting and premeal blood glucose (BG; < or = 6.7 mmol/l). Both groups will aim for a target hemoglobin AlC (AlC) of < 7%. ANTICIPATED RESULTS: The anticipated difference in PPBG (approximately 2.0 to 2.5 mM) between strategies is expected to demonstrate a 15% to 18.5% relative risk reduction in CV events for the postprandial strategy. CONCLUSION: This study may provide practical insights into the clinical management of patients with diabetes who have an increased risk of recurrent CV events and death.

A successful diabetes prevention study in Eskimos: the Alaska Siberia project.

OBJECTIVES: To test the efficacy of a simple intervention method to reduce risk factors for type 2 diabetes (DM) and cardiovascular disease (CVD) in Alaskan Eskimos. STUDY DESIGN: The study consisted of 1) a comprehensive screening for risk factors of 454 individuals in 4 villages, 2) a 4-year intervention and 3) a repetition of the screening in year 5 to test the efficacy of the intervention. METHODS: Personal counseling (1hr/year) stressed the consumption of more traditional foods high in omega-3 fatty acids and less of certain specific store-bought foods high in palmitic acid, which was identified as being associated with glucose intolerance. RESULTS: The intervention resulted in significant reductions in plasma concentrations of total cholesterol (p = 0.0001), LDL cholesterol (p = 0.0001), fasting glucose (p = 0.0001), diastolic blood pressure (p = 0.0007) and improved glucose tolerance (p = 0.0006). This occurred without loss of body weight. Sixty percent of the participants had improved glucose tolerance; only one of the 44 originally identified with impaired glucose tolerance (IGT) developed DM during the study. CONCLUSIONS: Dramatic improvements of risk factors for DM and CVD were achieved in the intervention by primarily stressing the need for changes in the consumption of specific fats. The results suggest that fat consumption is an important risk factor for DM.

Cardiovascular disease and risk factors in three Alaskan Eskimo populations: the Alaska-Siberia project.

OBJECTIVES: To determine the prevalence of CVD and to identify and characterize associated risk factors in three distinct Eskimo populations. STUDY DESIGN: Cross-sectional. METHODS: A slightly modified Strong Heart Study protocol was followed to examine 454 participants, aged 25-91, from four villages. RESULTS: Overall, 6% of the participants under 55 years of age and 26% of those > or = 55 years of age showed evidence of CHD by ECG, or in patient records. The prevalence of "definite coronary heart disease" (CHD) in women with glucose intolerance (GI) was 21.0%, compared to 2.4% in those with normal glucose tolerance (NGT). Men had comparable values of 26.7% and 6.3%. In addition, comparable values for "possible CHD" were 29.7% vs 6.0% for women and 21.4% vs 8.0% for men. GI was associated with relatively higher prevalences of CHD in women than in men (prevalence ratio = 8.5 vs 4.3). CHD was significantly related to age, glucose intolerance and insulin. Hypertension and obesity were significantly associated with CHD only in some ethnic groups. The prevalence of current smokers was 56%. CONCLUSIONS: Recent changes in lifestyle and diet of Alaskan Eskimos, leading to obesity, hypertension, insulin resistance and DM, contribute to an increased risk for cardiovascular disease.

A genetic and epidemiologic study of cardiovascular disease in Alaska natives (GOCADAN): design and methods.

This article is a report of the design and methods of the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) Study. This longitudinal, population-based study was initiated to investigate the genetic determinants of cardiovascular disease and its risk factors. Between October 2000 and April 2004, this family study enrolled 1,214 Eskimos from several coastal villages in the Norton Sound region of Western Alaska. Examinations included a physical, laboratory determinations, and measures of subclinical disease. This study will generate a genome-wide scan for loci influencing cardiovascular disease-related traits. Relations between subclinical atherosclerosis and markers of inflammation will be examined using historic and newly drawn samples. The study will provide data on CVD prevalence, risk factors and the relative contribution of genetic and environmental determinants in Alaska Native peoples. Data from this study will contribute to the delivery of health-care and prevention of CVD in Alaska Eskimos and other populations.

Albuminuria in recent-onset type 2 diabetes: the Strong Heart Study.

OBJECTIVE: It is not known how frequently abnormal albumin excretion occurs in the initial years after the onset of type 2 diabetes and to what extent its occurrence is related to the severity of diabetes. We have used a prospective cohort study to examine this. RESEARCH DESIGN AND METHODS: A total of 782 participants from the Strong Heart Study who had normal glucose tolerance and normal albumin excretion (albumin-to-creatinine ratio <30 mg albumin/g creatinine) at baseline were assessed for diabetes and abnormal albumin excretion at a follow-up visit (interval 3.91 +/- 0.95 years, mean +/- SD). Logistic regression models were used to examine the associations. RESULTS: Abnormal albumin excretion was detected in 52 (6.6%) and diabetes was determined to be present in 105 (13.4%) of the participants at the follow-up visit. In univariate analyses, abnormal albumin excretion was statistically significantly related to the baseline albumin-to-creatinine ratio, diastolic blood pressure, fasting insulin, and extent of American Indian heritage. Abnormal albumin excretion was much more prevalent in those with recent onset diabetes at the follow-up visit (18 vs. 5%, P < 0.001). In a logistic regression analysis, abnormal albumin excretion and diabetes remained strongly related (odds ratio 3.45, P < 0.001), and associations of abnormal albumin excretion with baseline albumin-to-creatinine ratio, blood pressure, and American Indian heritage also remained significant in a separate logistic regression analysis, including only those who developed diabetes. There was a strong association between abnormal albumin excretion and fasting glucose levels (<0.01) at the follow-up visit. CONCLUSIONS: These data suggest that an appreciable percentage of individuals develop abnormal albumin excretion within the first few years after the onset of type 2 diabetes. Also, the severity of diabetes at onset appears to be a key risk factor for the early development of abnormal albumin excretion.

Impact of computer-generated personalized goals on HbA(1c).

OBJECTIVE: The public is increasingly aware of the importance of HbA(1c) testing, yet the vast majority of patients with diabetes do not know their HbA(1c) status or goal. We set forth to evaluate the impact of a system that provides uniquely formatted and personalized reports of diabetes status and goals on changes in HbA(1c) levels. RESEARCH DESIGN AND METHODS: A total of 150 patients with diabetes were randomized to receive either standard care or intervention inclusive of a computer-generated 11" x 17" color poster depicting an individual's HbA(1c) status and goals along with personalized steps to aid in goal achievement. All patients enrolled received diabetes education during the 3 months before enrollment. HbA(1c) was performed at baseline and 6 months. RESULTS: At baseline, there were no significant differences between patient groups in terms of age, sex, education level, race, and HbA(1c) or lipid levels. Among patients with baseline HbA(1c) > or =7.0%, there was an 8.6% (0.77% absolute) reduction in HbA(1c) among control subjects compared with a 17.0% (1.69% absolute) decline in the intervention group (P = 0.032). There were no differences between the control and intervention groups with respect to the frequency of patients experiencing any decline in HbA(1c) (63 vs. 69%, P = 0.87); among these patients experiencing a decline, the most substantial reductions were seen with the control group, which had a 13.3% (1.15% absolute) decline compared with the intervention patients, who reduced their HbA(1c) by 24.2% (2.26% absolute reduction; P = 0.0048). At study close, 77% of the patients had their poster displayed on their refrigerator. CONCLUSIONS: This unique and personalized computer-generated intervention resulted in HbA(1c) lowering comparable to that of hypoglycemic agents.

Relation of left ventricular hypertrophy to inflammation and albuminuria in adults with type 2 diabetes: the strong heart study.

OBJECTIVE: To evaluate in adults with type 2 diabetes the extent to which the relation of left ventricular hypertrophy (LVH) to markers of systemic inflammation (fibrinogen and high-sensitivity C-reactive protein [hsCRP]) are affected by microangiopathy. RESEARCH DESIGN AND METHODS: We selected adults with type 2 diabetes using American Diabetes Association criteria from a population-based cohort, excluding those with medical history or electrocardiographic evidence of coronary heart disease or dialysis-dependent renal failure. LVH was assessed by echocardiogram. RESULTS: Of the 1299 eligible participants, 384 (29.6%) had LVH, which was associated with higher BMI, hsCRP, fibrinogen, and albuminuria in univariate analyses. After controlling for significant confounders, fibrinogen and albuminuria were higher in the presence of LVH (both P < 0.01), whereas hsCRP was not (P = 0.2), mostly because of the confounding effect of BMI. Adjustment for albuminuria abolished the relation of LVH to higher fibrinogen (P = 0.2). However, fibrinogen was significantly higher in participants with LVH among those without pathologic levels of albuminuria (<30 mg/g creatinuria), but not independent of BMI. Although hsCRP and fibrinogen were moderately correlated, fibrinogen, but not CRP, showed a significant relation with albuminuria. CONCLUSIONS: In adults with type 2 diabetes, echocardiographic LVH is associated with susceptibility to atherothrombosis and increased albuminuria, which is a marker of microangiopathy and endothelial dysfunction that appears in turn to be a relevant pathogenetic link between LVH and inflammation. However, in the absence of significant microalbuminuria, elevated BMI is a relevant pathogenetic factor in the relation of LVH to increased levels of markers of inflammation, potentially preceding development of significant albuminuria. In the presence of microangiopathy, we found that the atherothrombotic risk profile associated with LVH was independent of BMI and possibly reflected the association of LVH with a higher degree of endothelial dysfunction.

Non-HDL cholesterol as a predictor of cardiovascular disease in type 2 diabetes: the strong heart study.

OBJECTIVE: To determine whether non-HDL cholesterol, a measure of total cholesterol minus HDL cholesterol, is a predictor of CVD in patients with diabetes. RESEARCH DESIGN AND METHODS: The Strong Heart Study, a population-based study of CVD and its risk factors in 13 American Indian communities in three geographic areas in the U.S. The baseline examination, conducted between July 1989 and January 1992, consisted of a personal interview, a physical examination, and laboratory tests. Of the 4,549 women and men aged 45-74 years participating in the study, 2,108 had diabetes but no CVD at baseline. Data on fatal and nonfatal CVD were collected during the follow-up period through 31 December 1998 (average 9 years). RESULTS: Multivariable analyses indicated that non-HDL cholesterol is a strong predictor of CVD in men and women with diabetes and is particularly indicative of coronary events. Hazard ratios for the highest tertile of non-HDL cholesterol in men and women with diabetes (2.23 and 1.80, respectively) were higher than those for either LDL cholesterol or triglycerides alone in both men and women and were higher than the ratio of total/HDL cholesterol in women. The utility of non-HDL cholesterol in predicting CVD extended over a wide range of triglyceride concentrations. CONCLUSIONS: This study suggests that non-HDL cholesterol index may be particularly useful in predicting CVD risk in patients with diabetes.