Long-Term Complications in Youth-Onset Type 2 Diabetes.

BACKGROUND: The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood. METHODS: We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated. RESULTS: At the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up. CONCLUSIONS: Among participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).

Racial differences in all-cause mortality and future complications among people with diabetes: a systematic review and meta-analysis of data from more than 2.4 million individuals.

AIMS/HYPOTHESIS: The aim of this work was to quantify racial/ethnic differences in risk for future diabetic complications and all-cause mortality by performing a meta-analysis of prospective studies. METHODS: A systematic search in PubMed and EMBASE was performed from inception to May 2021. Prospective cohort studies that reported HRs and associated 95% CIs of diabetes complications and all-cause mortality among racial/ethnic groups, with White people as the reference group, were included. Study characteristics and HR estimates were extracted from each study. Estimates were pooled using random-effects inverse-variance model with the Hartung-Knapp-Sidik-Jonkman variance estimator. RESULTS: A total of 23 studies were included, comprising 2,416,516 individuals diagnosed with diabetes (White 59.3%, Black 11.2%, Asian 1.3%, Hispanic-American 2.4%, Native American 0.2%, East Asian 1.9%, South Asian 0.8%, Pacific Islander 2.3%, Maori 2.4% and others 18.2%). Compared with White individuals with diabetes, individuals of Maori ethnicity were at higher risk for all-cause mortality (HR 1.88 [95% CI 1.61, 2.21]; I2 = 7.1%), Hispanic-American individuals had a significantly lower risk for CVD (HR 0.66 [95% CI 0.53, 0.81]; I2 = 0%) and Black individuals had higher risk for end-stage renal disease (HR 1.54 [95% CI 1.05, 2.24]; I2 = 95.4%). No significant higher risk for diabetes complications was found in other racial/ethnic groups relative to White people. CONCLUSIONS/INTERPRETATION: Racial/ethnic differences exist in the risk for future diabetic complications and all-cause mortality. Our results support the use of such categories for international diabetes clinical guideline recommendations until better predictors become available. Efforts to identify high-risk groups and to better control cardiovascular risk factors across ethnically diverse populations are therefore needed. REGISTRATION: PROSPERO registration ID CRD42021239274.

Diabetes-related lower extremity complications in a multi-ethnic Asian population: a 10 year observational study in Singapore.

AIMS/HYPOTHESIS: Diabetes progression and complication risk are different in Asian people compared with those of European ancestry. In this study, we sought to understand the epidemiology of diabetes-related lower extremity complications (DRLECs: symptomatic peripheral arterial disease, ulceration, infection, gangrene) and amputations in a multi-ethnic Asian population. METHODS: This was a retrospective observational study using data obtained from one of three integrated public healthcare clusters in Singapore. The population consisted of individuals with incident type 2 diabetes who were of Chinese, Malay, Indian or Other ethnicity. We examined incidence, time to event and risk factors of DRLECs and amputation. RESULTS: Between 2007 and 2017, of the 156,593 individuals with incident type 2 diabetes, 20,744 developed a DRLEC, of whom 1208 underwent amputation. Age- and sex-standardised incidence of first DRLEC and first amputation was 28.29/1000 person-years of diabetes and 8.18/1000 person-years of DRLEC, respectively. Incidence of both was highest in individuals of Malay ethnicity (DRLEC, 36.09/1000 person-years of diabetes; amputation, 12.96/1000 person-years of DRLEC). Median time from diabetes diagnosis in the public healthcare system to first DRLEC was 30.5 months for those without subsequent amputation and 10.9 months for those with subsequent amputation. Median time from DRLEC to first amputation was 2.3 months. Older age (p < 0.001), male sex (p < 0.001), Malay ethnicity (p < 0.001), Indian ethnicity (p = 0.014), chronic comorbidities (nephropathy [p < 0.001], heart disease [p < 0.001], stroke [p < 0.001], retinopathy [p < 0.001], neuropathy [p < 0.001]), poorer or missing HbA1c (p < 0.001), lower (p < 0.001) or missing (p = 0.002) eGFR, greater or missing BMI (p < 0.001), missing LDL-cholesterol (p < 0.001) at diagnosis, and ever-smoking (p < 0.001) were associated with higher hazard of DRLEC. Retinopathy (p < 0.001), peripheral vascular disease (p < 0.001), poorer HbA1c (p < 0.001), higher (p = 0.009) or missing (p < 0.001) LDL-cholesterol and missing BMI (p = 0.008) were associated with higher hazard of amputation in those with DRLEC. Indian ethnicity (p = 0.007) was associated with significantly lower hazard of amputation. CONCLUSIONS/INTERPRETATION: This study has revealed important ethnic differences in risk of diabetes-related lower limb complications, with Malays most likely to progress to DRLEC. Greater research efforts are needed to understand the aetiopathological and sociocultural processes that contribute to the higher risk of lower extremity complications among these ethnic groups.

Epidemiology and Risk of Amputation in Patients With Diabetes Mellitus and Peripheral Artery Disease.

Peripheral artery disease (PAD) stems from atherosclerosis of lower extremity arteries with resultant arterial narrowing or occlusion. The most severe form of PAD is termed chronic limb-threatening ischemia and carries a significant risk of limb loss and cardiovascular mortality. Diabetes mellitus is known to increase the incidence of PAD, accelerate disease progression, and increase disease severity. Patients with concomitant diabetes mellitus and PAD are at high risk for major complications, such as amputation. Despite a decrease in the overall number of amputations performed annually in the United States, amputation rates among those with both diabetes mellitus and PAD have remained stable or even increased in high-risk subgroups. Within this cohort, there is significant regional, racial/ethnic, and socioeconomic variation in amputation risk. Specifically, residents of rural areas, African-American and Native American patients, and those of low socioeconomic status carry the highest risk of amputation. The burden of amputation is severe, with 5-year mortality rates exceeding those of many malignancies. Furthermore, caring for patients with PAD and diabetes mellitus imposes a significant cost to the healthcare system-estimated to range from $84 billion to $380 billion annually. Efforts to improve the quality of care for those with PAD and diabetes mellitus must focus on the subgroups at high risk for amputation and the disparities they face in the receipt of both preventive and interventional cardiovascular care. Better understanding of these social, economic, and structural barriers will prove to be crucial for cardiovascular physicians striving to better care for patients facing this challenging combination of chronic diseases.

High prevalence of Afro-Caribbean ethnicity and hypoglycaemia in patients with diabetes and end stage renal disease hospitalized with COVID-19.

End stage renal disease (ESRD) is associated with a high mortality rate among patients hospitalized with COVID-19. To the best of our knowledge, there is limited data on the clinical features, ethnicity, inpatient glycaemic control and outcomes in patients with diabetes related ESRD in the literature. We report the clinical features and outcomes of 39 consecutive ESRD patients (28 on haemodialysis [HD] and 11 with renal transplant) secondary to diabetic kidney disease admitted to a university hospital with COVID-19. We observed a high prevalence of patients of Afro-Caribbean ethnicity hospitalized with COVID-19 with a 73% and 54% prevalence in renal transplant and HD groups respectively. The mortality rate of our cohort was 36%. Nearly a one-third of HD patients and one-fifth of transplant patients had hypoglycaemic events during COVID-19 hospitalization. Adjustment of diabetes treatment was frequently required. Our data highlight the importance of integrated multidisciplinary care of patients with diabetes related ESRD hospitalized with COVID-19.

Ethnicity and Type 2 diabetes in the UK.

Type 2 diabetes is a major UK public health priority. Among minority ethnic communities, the prevalence is alarmingly high, approximately three to five times higher than in the white British population. Particularly striking is the earlier onset of Type 2 diabetes, which occurs some 10-12 years younger, with a significant proportion of cases being diagnosed before the age of 40 years. This review focuses on the UK context and Type 2 diabetes in adult populations, exploring the available evidence regarding the complex interplay of biological, lifestyle, social, clinical and healthcare system factors that are known to drive these disparities.

Real-world opportunity of empagliflozin to improve blood pressure control in African American patients with type 2 diabetes: A National Cardiovascular Data Registry "research-to-practice" project from the diabetes collaborative registry.

The 1245.29 Trial recently showed that empaglifozin improved both blood pressure and glucose control in African American (AA) patients with type 2 diabetes (T2D) and hypertension. Using the Diabetes Collaborative Registry, a large-scale US registry of outpatients with diabetes recruited from primary care, cardiology and endocrinology practices, we sought to understand the potential impact of these observations in routine clinical practice. Among 74 290 AA patients with T2D from 368 US clinics, 60.4% had hypertension, of whom 34.5% had systolic blood pressure ≥ 140 mm Hg (20.8% of the total AA T2D population). Only 1.7% of this eligible population had been prescribed a sodium-glucose co-transporter two inhibitor. The mean estimated 5-year risk of cardiovascular death was 7.7%, which could be reduced to 6.2% when modelling the antihypertensive effect of empagliflozin across the eligible population (based on an 8-mm Hg blood pressure reduction). These findings may represent a potential opportunity for better management of cardiovascular risk factors and improved outcomes in this vulnerable cohort.

Age Disparities Among Patients With Type 2 Diabetes and Associated Rates of Hospital Use and Diabetic Complications.

INTRODUCTION: Although screening for diabetes is recommended at age 45, some populations may be at greater risk at earlier ages. Our objective was to quantify age disparities among patients with type 2 diabetes in New York City. METHODS: Using all-payer hospital claims data for New York City, we performed a cross-sectional analysis of patients with type 2 diabetes identified from emergency department visits during the 5-year period 2011-2015. We estimated type 2 diabetes prevalence at each year of life, the age distribution of patients stratified by decade, and the average age of patients by sex, race/ethnicity, and geographic location. RESULTS: We identified 576,306 unique patients with type 2 diabetes. These patients represented more than half of all people with type 2 diabetes in New York City. Patients in racial/ethnic minority groups were on average 5.5 to 8.4 years younger than non-Hispanic white patients. At age 45, type 2 diabetes prevalence was 10.9% among non-Hispanic black patients and 5.2% among non-Hispanic white patients. In our geospatial analyses, patients with type 2 diabetes were on average 6 years younger in hotspots of diabetes-related emergency department use and inpatient hospitalizations. The average age of patients with type 2 diabetes was also 1 to 2 years younger in hotspots of microvascular diabetic complications. CONCLUSION: We identified profound age disparities among patients with type 2 diabetes in racial/ethnic minority groups and in neighborhoods with poor health outcomes. The younger age of these patients may be due to earlier onset of diabetes and/or earlier death from diabetic complications. Our findings demonstrate the need for geographically targeted interventions that promote earlier diagnosis and better glycemic control.

The association of metformin use with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study.

PURPOSE: Metformin has been associated with a reduced incidence of prostate cancer and improved prostate cancer outcomes. However, whether race modifies the association between metformin use and prostate cancer aggressiveness remains uncertain. The association between metformin use and prostate cancer aggressiveness was examined separately in Black Americans (Blacks) and White Americans (Whites). METHODS: The study population consisted of 305 Black and 195 White research participants with incident prostate cancer and self-reported diabetes from the North Carolina-Louisiana Prostate Cancer Project. High-aggressive prostate cancer was defined using a composite measure of Gleason sum, prostate-specific antigen, and clinical stage. Multivariable logistic regression was used to assess the association between metformin use and high-aggressive prostate cancer at diagnosis, separately among Whites and Blacks, with adjustment for age, screening history, site, education, insurance, and body mass index. RESULTS: Metformin use was associated positively with high-aggressive prostate cancer in Blacks (OR 2.01; 95% CI 1.05, 3.83). By contrast, a weak inverse association between metformin use and high-aggressive prostate cancer was found in Whites (OR 0.80, 95% CI 0.34, 1.85). CONCLUSIONS: The association between metformin use and prostate cancer aggressiveness may be modified by race.

Prevalence and incidence of complications at diagnosis of T2DM and during follow-up by BMI and ethnicity: a matched case-control analysis.

AIMS: To estimate the risk of developing long-term major cardiovascular and renal complications in relation to levels of body mass index (BMI) in a population of White European (WE), African-Caribbean (AC), and South Asian (SA) patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Patients with new diagnosis of T2DM, aged ≥ 18 years from January 2000 (n = 69,436) and their age-sex-ethnicity matched non-diabetic controls (n = 272,190) were identified from UK primary care database. Incidence rates ratios (IRRs) for non-fatal major cardiovascular events (MACE) and chronic kidney disease (CKD) in patients with T2DM compared to controls were estimated using multivariate Mantel-Cox model. RESULTS: Among normal weight patients with T2DM, WEs had significantly higher prevalence of cardiovascular multi-morbidity (95% CI 9.5, 11.3), compared to SAs (95% CI 4.8, 9.5). AC and SA overweight and obese patients had similar prevalence, while obese WEs had significantly higher prevalence. During a median 7 years of follow-up, risk of MACE was significantly higher for overweight (95% CI of IRR 1.50, 2.46) and obese (95% CI of IRR 1.49, 2.43) SAs compared to their WE counterparts. However, similar risk levels were observed for normal weight WEs and SAs, respectively. Risk of CKD was higher and uniform for BMI ≥ 25 kg/m2 amongst WEs and ACs, whereas only overweight patients had significantly higher risk of CKD amongst SA [IRR 2.08 (95% CI 1.49, 2.93)]. CONCLUSION: Risk of MACE/CKD varies over levels of BMI within each ethnic group, with overweight SAs having a disproportionate risk of CKD.

Blood-based bioenergetic profiling is related to differences in brain morphology in African Americans with Type 2 diabetes.

Blood-based bioenergetic profiling has promising applications as a minimally invasive biomarker of systemic bioenergetic capacity. In the present study, we examined peripheral blood mononuclear cell (PBMC) mitochondrial function and brain morphology in a cohort of African Americans with long-standing Type 2 diabetes. Key parameters of PBMC respiration were correlated with white matter, gray matter, and total intracranial volumes. Our analyses indicate that these relationships are primarily driven by the relationship of systemic bioenergetic capacity with total intracranial volume, suggesting that systemic differences in mitochondrial function may play a role in overall brain morphology.

Type 2 diabetes in young adults in Central Auckland: demography and complications.

BACKGROUND: Type 2 diabetes (T2D) in young adults is associated with a high risk of diabetes complications. AIMS: To investigated the demography and the emergence of complications of young adults with T2D in the central Auckland region where there has been substantial immigration. METHODS: In total, 310 young adults with T2D (<40 years) were registered with the Auckland Diabetes Centre in 2015. We documented demographic, anthropometric and metabolic variables and prevalence and the emergence of complications. RESULTS: Three demographic groups accounted for 243 participants (78%): 135 (44%) were migrants of Asian or Pacific Island origin, diagnosed a median 9 years after migration at a mean age of 28 ± 6 years; 88 (29%) were New Zealand-born Pasifika descent, with a high prevalence of morbid obesity and 37 (12%) had major mental illness or intellectual disability. At diagnosis, the median HbA1c was 80 mmol/mol, and in 28%, it was ≥100 mmol/mol. A median 6 years after diagnosis, 56% had some degree of retinopathy, with the prevalence related both to the duration of diabetes and glycaemic control (P = 0.001). Forty-four percent of subjects had abnormal albuminuria at diagnosis (12% with macroalbuminuria). Increased albuminuria was strongly associated with obesity (P = 0.002). The development of CKD stages 4-5 was related both to the severity of retinopathy and degree of albuminuria at diagnosis (P = 0.0001). Major cardiovascular events were related to the severity of retinopathy at diagnosis (P = 0.0001). CONCLUSIONS: New migrants, New Zealand-born Pasifika and patients with mental illness or an intellectual disability comprise the bulk of young onset T2D. The disease is aggressive, and by the age of 40, patients are already developing advanced complications.

The Impact of Diabetes on Patient Outcomes After Total Knee Arthroplasty in an Asian Population.

BACKGROUND: Diabetes is implicated with poorer outcomes and more complications after total knee arthroplasty (TKA). We aim to determine whether diabetes affects infection risk, functional outcomes, patient-reported outcome measures, and patient satisfaction in Asian patients after TKA. METHODS: Prospectively collected data for 905 patients who underwent unilateral TKA by a single surgeon from February 2004 to July 2014 were reviewed, of which 123 (13.6%) patients suffered from diabetes. At 2-year follow-up, the change in range of motion of the operated knee, body mass index, Knee Society Score, Oxford Knee Score (OKS), and Short Form-36 from baseline was compared between diabetic and nondiabetic patients. We also analyzed the length of hospitalization stay, infection risk, and patient satisfaction between the 2 groups. RESULTS: Compared with nondiabetic patients, diabetic patients had significantly poorer preoperative OKS (37.6 on 8.3 to 35.8 .38.0, P = .02) and Short Form-36 Mental Component Score (48.3 Me11.2 to 51.7 1.10.7, P = .01). At 2-year follow-up, diabetes continued to be associated with poorer OKS of 21.2 018.4 and Knee Society Score Function score of 64.7 Fu20.9 compared to 19.1 0.6.2 (P = .02) and 71.8 0220.1 (P = .01) respectively in nondiabetic patients. Interestingly, the difference in mental well-being was no longer significant after TKA. A significantly larger proportion of diabetic patients (50%) had a reduction in body mass index after TKA compared to 36% in nondiabetic patients (P < .01). There was no difference in range of motion, length of hospitalization stay, infection risk, and patient satisfaction. CONCLUSION: Despite poorer physical scores throughout, diabetic patients are no less satisfied and had significantly greater improvement in mental well-being and weight reduction after surgery.

Association between grip strength and diabetes prevalence in black, South-Asian, and white European ethnic groups: a cross-sectional analysis of 418 656 participants in the UK Biobank study.

AIMS: To quantify the extent to which ethnic differences in muscular strength might account for the substantially higher prevalence of diabetes in black and South-Asian compared with white European adults. METHODS: This cross-sectional study used baseline data from the UK Biobank study on 418 656 white European, black and South-Asian participants, aged 40-69 years, who had complete data on diabetes status and hand-grip strength. Associations between hand-grip strength and diabetes were assessed using logistic regression and were adjusted for potential confounding factors. RESULTS: Lower grip strength was associated with higher prevalence of diabetes, independent of confounding factors, across all ethnicities in both men and women. Diabetes prevalence was approximately three- to fourfold higher in South-Asian and two- to threefold higher in black participants compared with white European participants across all levels of grip strength, but grip strength in South-Asian men and women was ~ 5-6 kg lower than in the other ethnic groups. Thus, the attributable risk for diabetes associated with low grip strength was substantially higher in South-Asian participants (3.9 and 4.2 cases per 100 men and women, respectively) than in white participants (2.0 and 0.6 cases per 100 men and women, respectively). Attributable risk associated with low grip strength was also high in black men (4.3 cases) but not in black women (0.4 cases). CONCLUSIONS: Low strength is associated with a disproportionately large number of diabetes cases in South-Asian men and women and in black men. Trials are needed to determine whether interventions to improve strength in these groups could help reduce ethnic inequalities in diabetes prevalence.

Vital Signs: Decrease in Incidence of Diabetes-Related End-Stage Renal Disease among American Indians/Alaska Natives - United States, 1996-2013.

BACKGROUND: American Indians and Alaska Natives (AI/AN) have the highest diabetes prevalence among any racial/ethnic group in the United States. Among AI/AN, diabetes accounts for 69% of new cases of end-stage renal disease (ESRD), defined as kidney failure treated with dialysis or transplantation. During 1982-1996, diabetes-related ESRD (ESRD-D) in AI/AN increased substantially and disproportionately compared with other racial/ethnic groups. METHODS: Data from the U.S. Renal Data System, the Indian Health Service (IHS), the National Health Interview Survey, and the U.S. Census were used to calculate ESRD-D incidence rates by race/ethnicity among U.S. adults aged ≥18 years during 1996-2013 and in the diabetic population during 2006-2013. Rates were age-adjusted based on the 2000 U.S. standard population. IHS clinical data from the Diabetes Cares and Outcomes Audit were analyzed for diabetes management measures in AI/AN. RESULTS: Among AI/AN adults, age-adjusted ESRD-D rates per 100,000 population decreased 54%, from 57.3 in 1996 to 26.5 in 2013. Although rates for adults in other racial/ethnic groups also decreased during this period, AI/AN had the steepest decline. Among AI/AN with diabetes, ESRD-D incidence decreased during 2006-2013 and, by 2013, was the same as that for whites. Measures related to the assessment and treatment of ESRD-D risk factors also showed more improvement during this period in AI/AN than in the general population. CONCLUSION AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Despite well-documented health and socioeconomic disparities among AI/AN, ESRD-D incidence rates among this population have decreased substantially since 1996. This decline followed implementation by the IHS of public health and population management approaches to diabetes accompanied by improvements in clinical care beginning in the mid-1980s. These approaches might be a useful model for diabetes management in other health care systems, especially those serving populations at high risk.

Latent class analysis suggests four classes of persons with type 2 diabetes mellitus based on complications and comorbidities in Tianjin, China: a cross-sectional analysis.

The aim of this study was to explore a new classification way in persons with type 2 diabetes mellitus based on complications and comorbidities using Latent Class Analysis, moreover, finding out the factors associated with different latent classes and making specific suggestions. In this study, 5,500 patients with type 2 diabetes mellitus from ten hospitals in Tianjin, China were selected, and the response rate was 96.2%. Latent Class Analysis was used to cluster patients. After compared the baseline characteristics, multinomial logistic regression was applied. Patients with type 2 diabetes mellitus were classified into four classes. In the univariate analysis, all variables were significant (p<0.05). According to multinomial logistic regression, we found longer duration of type 2 diabetes mellitus, family history of diabetes, older age, obesity and central obesity, female menopause, living in a suburb, having a higher 2hPG at diagnosis, smoking and drinking were associated with the prevalence of complications and comorbidities. In conclusion, LCA was shown to be an effective method for grouping patients with T2DM, which presented a nuanced approach to data reduction. Further research using LCA may be especially useful to investigate causal relationships between complications and the significant factors identified in our study.

Association of multiple chronic conditions and pain among older black and white adults with diabetes mellitus.

BACKGROUND: Aging is often associated with the challenge of navigating daily tasks with a painful chronic medical illness. Yet, there is concern of the number of older adults impacted with more than one chronic condition. Despite the increasing number of adults diagnosed with diabetes and comorbid chronic illnesses, there remains a lack of understanding in how multiple illnesses relate to experiences of pain. To assess the association between multiple chronic conditions and pain, this study aimed to identify clusters of chronic medical conditions and their association with pain among a sample of older Black and White adults diagnosed with diabetes. METHODS: Two hundred and thirty-six participants responded to a series of questions assessing pain frequency and severity, as well as health and social characteristics. A factor analysis was used to categorize clusters of medical conditions, and multiple regression models were used to examine predictors of pain. RESULTS: Seven of the assessed chronic medical conditions loaded on three factors, and accounted for 57.2% of the total variance, with heart disease (factor 1) accounting for 21.9%, musculoskeletal conditions (factor 2) for another 18.4%, and factor 3 (microvascular diseases) accounting for a final 16.9% of the variability among the chronic medical conditions. Covariate-adjusted models showed that fewer years of education and higher scores on the microvascular and musculoskeletal conditions factors were associated with higher pain frequency, with the musculoskeletal conditions factor being the strongest predictor. CONCLUSIONS: Findings from this study compliment existent literature underscoring the prevalence and importance of comorbid diagnoses in relation to pain. Examining health-related factors beyond a single disease diagnosis also provides an opportunity to explore underlying disease co-occurrences that may persist beyond organ system classifications.

Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans.

INTRODUCTION: African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. METHODS: We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs. RESULTS: Two SNPs at novel loci, rs112404845 (P = 3.8 × 10-8), upstream of COBL, and rs16961023 (P = 4.6 × 10-8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability. DISCUSSION: An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.

Glucose level decline precedes dementia in elderly African Americans with diabetes.

INTRODUCTION: High blood glucose levels may be responsible for the increased risk for dementia in diabetic patients. METHODS: A secondary data analysis merging electronic medical records (EMRs) with data collected from the Indianapolis-Ibadan Dementia project (IIDP). Of the enrolled 4105 African Americans, 3778 were identified in the EMR. Study endpoints were dementia, mild cognitive impairment (MCI), or normal cognition. Repeated serum glucose measurements were used as the outcome variables. RESULTS: Diabetic participants who developed incident dementia had a significant decrease in serum glucose levels in the years preceding the diagnosis compared to the participants with normal cognition (P = .0002). They also had significantly higher glucose levels up to 9 years before the dementia diagnosis (P = .0367). DISCUSSION: High glucose levels followed by a decline occurring years before diagnosis in African American participants with diabetes may represent a powerful presymptomatic metabolic indicator of dementia.