First and second branchial arch involvement in mandibulofacial dysostosis Guion-Almeida type.

BACKGROUND: Mandibulofacial dysostosis Guion-Almeida Type (MFDGA; OMIM#610536) is a rare autosomal dominant genetic disorder caused by heterozygous pathogenic variants in the EFTUD2 gene. Mandibulofacial dysostoses are characterised by the core triad malar hypoplasia, maxillary hypoplasia and dysplastic ears, all derived by the impaired development of the first and second branchial arches. Differential diagnosis is often challenging. The early genetic diagnosis is extremely useful, not only for the correct management of cranial malformations, but also for the early diagnosis and treatment of the comorbidities associated to the disease, which greatly benefit from early treatment.

Improved clinical utility of preimplantation genetic testing through the integration of ploidy and common pathogenic microdeletions analyses.

STUDY QUESTION: Can chromosomal abnormalities beyond copy-number aneuploidies (i.e. ploidy level and microdeletions (MDs)) be detected using a preimplantation genetic testing (PGT) platform? SUMMARY ANSWER: The proposed integrated approach accurately assesses ploidy level and the most common pathogenic microdeletions causative of genomic disorders, expanding the clinical utility of PGT. WHAT IS KNOWN ALREADY: Standard methodologies employed in preimplantation genetic testing for aneuploidy (PGT-A) identify chromosomal aneuploidies but cannot determine ploidy level nor the presence of recurrent pathogenic MDs responsible for genomic disorders. Transferring embryos carrying these abnormalities can result in miscarriage, molar pregnancy, and intellectual disabilities and developmental delay in offspring. The development of a testing strategy that integrates their assessment can resolve current limitations and add valuable information regarding the genetic constitution of embryos, which is not evaluated in PGT providing new level of clinical utility and valuable knowledge for further understanding of the genomic causes of implantation failure and early pregnancy loss. To the best of our knowledge, MDs have never been studied in preimplantation human embryos up to date. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort analysis including blastocyst biopsies collected between February 2018 and November 2021 at multiple collaborating IVF clinics from prospective parents of European ancestry below the age of 45, using autologous gametes and undergoing ICSI for all oocytes. Ploidy level determination was validated using 164 embryonic samples of known ploidy status (147 diploids, 9 triploids, and 8 haploids). Detection of nine common MD syndromes (-4p=Wolf-Hirschhorn, -8q=Langer-Giedion, -1p=1p36 deletion, -22q=DiGeorge, -5p=Cri-du-Chat, -15q=Prader-Willi/Angelman, -11q=Jacobsen, -17p=Smith-Magenis) was developed and tested using 28 positive controls and 97 negative controls. Later, the methodology was blindly applied in the analysis of: (i) 100 two pronuclei (2PN)-derived blastocysts that were previously defined as uniformly euploid by standard PGT-A; (ii) 99 euploid embryos whose transfer resulted in pregnancy loss. PARTICIPANTS/MATERIALS, SETTING, METHODS: The methodology is based on targeted next-generation sequencing of selected polymorphisms across the genome and enriched within critical regions of included MD syndromes. Sequencing data (i.e. allelic frequencies) were analyzed by a probabilistic model which estimated the likelihood of ploidy level and MD presence, accounting for both sequencing noise and population genetics patterns (i.e. linkage disequilibrium, LD, correlations) observed in 2504 whole-genome sequencing data from the 1000 Genome Project database. Analysis of phased parental haplotypes obtained by single-nucleotide polymorphism (SNP)-array genotyping was performed to confirm the presence of MD. MAIN RESULTS AND THE ROLE OF CHANCE: In the analytical validation phase, this strategy showed extremely high accuracy both in ploidy classification (100%, CI: 98.1-100%) and in the identification of six out of eight MDs (99.2%, CI: 98.5-99.8%). To improve MD detection based on loss of heterozygosity (LOH), common haploblocks were analyzed based on haplotype frequency and LOH occurrence in a reference population, thus developing two further mathematical models. As a result, chr1p36 and chr4p16.3 regions were excluded from MD identification due to their poor reliability, whilst a clinical workflow which incorporated parental DNA information was developed to enhance the identification of MDs. During the clinical application phase, one case of triploidy was detected among 2PN-derived blastocysts (i) and one pathogenic MD (-22q11.21) was retrospectively identified among the biopsy specimens of transferred embryos that resulted in miscarriage (ii). For the latter case, family-based analysis revealed the same MD in different sibling embryos (n = 2/5) from non-carrier parents, suggesting the presence of germline mosaicism in the female partner. When embryos are selected for transfer based on their genetic constitution, this strategy can identify embryos with ploidy abnormalities and/or MDs beyond aneuploidies, with an estimated incidence of 1.5% (n = 3/202, 95% CI: 0.5-4.5%) among euploid embryos. LIMITATIONS, REASONS FOR CAUTION: Epidemiological studies will be required to accurately assess the incidence of ploidy alterations and MDs in preimplantation embryos and particularly in euploid miscarriages. Despite the high accuracy of the assay developed, the use of parental DNA to support diagnostic calling can further increase the precision of the assay. WIDER IMPLICATIONS OF THE FINDINGS: This novel assay significantly expands the clinical utility of PGT-A by integrating the most common pathogenic MDs (both de novo and inherited ones) responsible for genomic disorders, which are usually evaluated at a later stage through invasive prenatal testing. From a basic research standpoint, this approach will help to elucidate fundamental biological and clinical questions related to the genetics of implantation failure and pregnancy loss of otherwise euploid embryos. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. S.C., M.F., F.C., P.Z., I.P., L.G., C.P., M.P., D.B., J.J.-A., D.B.-J., J.M.-V., and C.R. are employees of Igenomix and C.S. is the head of the scientific board of Igenomix. A.C. and L.P. are employees of JUNO GENETICS. Igenomix and JUNO GENETICS are companies providing reproductive genetic services. TRIAL REGISTRATION NUMBER: N/A.

Hyperglycemia is associated with relatively lower lean body mass in older adults.

BACKGROUND/OBJECTIVES: Older adults with known diabetes are vulnerable to accelerated loss of lean body mass. However, the relationship of hyperglycemia per se with lean body mass is not fully understood. We sought to examine the independent relationship of hyperglycemia with relative lean body mass in older persons without a reported history of diabetes. DESIGN: Cross-sectional nationally representative survey. SETTING: United States. PARTICIPANTS: We studied U.S. adults >50 years without known diabetes (n=5434) in the National Health and Nutrition Examination Survey (1999-2004). MEASUREMENTS: In linear regression models, we studied the relationship of measured HbA1c (<5.0%, 5.0-5.4%, 5.5-5.9%, 6.0-6.4%, ≥6.5%) with percent lean body mass, measured by dual-energy x-ray absorptiometry, after accounting for potential confounders. RESULTS: Among older U.S. men and women, progressively higher HbA1c was associated with relatively lower total, appendicular, and trunk percent lean mass, independent of demographics and height (all p<0.05). Accounting for physical activity, C-reactive protein, and diabetes-related comorbidities (heart disease, peripheral arterial disease, arthritis, neuropathy, hip fracture, amputation, cancer, pulmonary disease), undiagnosed diabetes (i.e. HbA1c ≥6.5%) versus reference (<5.0%) in both men and women was associated with lower total (-3.5±0.8% and -2.9±0.8%), appendicular (-1.8±0.5% and -1.2±0.4%), and trunk percent lean mass (-1.2±0.4% and -1.3±0.5%), respectively (all p<0.05). Persons at increased risk for diabetes (i.e. HbA1c 6.0-6.4%) also had significant decrements at these sites versus reference. CONCLUSIONS: Hyperglycemia is associated with relatively lower lean mass in a nationally representative population of older adults without history of diabetes. Future longitudinal studies are needed to investigate the relationship of hyperglycemia with the accelerated decline of skeletal muscle mass in older persons.

Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer.

Nectins are Ca(2+)-independent immunoglobulin-like cell adhesion molecules that compose a family of four members that regulate several cellular activities such as movement, proliferation, survival, differentiation, polarization, and the entry of viruses. Nectin-4 has recently emerged as a metastatis-associated protein in several cancers. Here, we have evaluated the association between the expression of Nectin-4 and the clinical outcome of patients with node-negative, T1/T2 breast cancers.The study group consisted of 197 patients presenting with primary unilateral breast carcinoma (T1/T2), with no evidence of nodal involvement and distant metastases. Nectin-4 protein expression was assessed by immunohistochemistry on tissue microarrays, and the results correlated with the clinical data using Kaplan-Meier curves and multivariate Cox regression analysis. Thirty-four out of 197 tumors (17.3%) exhibited Nectin-4 expression on cell membrane (m-Nectin-4) and 122 out of the 163m-Nectin-4 negative tumors (74.8%) showed high cytoplasmic expression of Nectin-4 (c-Nectin-4(High)). At Kaplan-Meier analysis, m-Nectin-4 positivity was significantly associated with a lower disease-free survival (DFS) and distant relapse-free survival (DRFS) rate in patients with a luminal-A phenotype (P=0.030 and P=0.002, respectively). Multivariate analysis showed that in luminal-A tumors m-Nectin-4 positivity is an independent prognostic factor for DFS (P=0.018) and DRFS (P=0.004), but not for local relapse-free survival (LRFS). On the other hand, c-Nectin-4(High) was significantly associated with higher rates of DFS and LRFS, but not DRFS, in the whole population (P=0.008 and P=0.004, respectively) and in patients with luminal-A tumors (P=0.022 and P=0.018, respectively). In patients with luminal-A tumors, multivariate analysis showed that the prognostic value of c-Nectin-4(Low/Negative) is limited to DFS (P=0.012) and LRFS (P=0.022). We suggest that Nectin-4 represents a prognostic factor and a therapeutic target in luminal-A early stage breast cancer.

Meta-analysis: vitamin D and non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition. Emerging evidence suggests that vitamin D may play a role in the pathogenesis of NAFLD. AIM: To review systematically the association between vitamin D levels, measured as serum 25-hydroxy vitamin D [25(OH)D], and NAFLD. METHODS: We used PubMed and EMBASE databases to identify all studies that assessed the association between vitamin D and NAFLD up until 22 April 2013, without language restrictions. We included studies that compared vitamin D levels between NAFLD cases and controls and also those that compared the odds of vitamin D deficiency by NAFLD status. Pooled standardised differences and odds ratios were calculated using an inverse variance method. RESULTS: Seventeen cross-sectional and case-control studies have evaluated the association between vitamin D and NAFLD. NAFLD was diagnosed using biopsy (4 studies), ultrasound or CT (10 studies) and liver enzymes (3 studies). Nine studies provided data for a quantitative meta-analysis. Compared to controls, NAFLD patients had 0.36 ng/mL (95% CI: 0.32, 0.40 ng/mL) lower levels of 25(OH)D and were 1.26 times more likely to be vitamin D deficient (OR 1.26, 95% CI: 1.17, 1.35). CONCLUSIONS: NAFLD patients have decreased serum 25(OH)D concentrations, suggesting that vitamin D may play a role in the development of NAFLD. The directionality of this association cannot be determined from cross-sectional studies. Demonstration of a causal role of hypovitaminosis D in NAFLD development in future studies could have important therapeutic implications.

Nectinopathies: an emerging group of ectodermal dysplasia syndromes.

Cleft Lip/Palate-Ectodermal Dysplasia and Ectodermal Dysplasia-Syndactyly Syndrome are rare congenital disorders caused by recessive mutations in the PVRL1 and PVRL4 genes, respectively. These genes encode nectins 1 and 4, an emerging class of molecules acting in cooperation with cadherins to form cell-cell adhesion especially at adherens junctions. Their role in skin, hair and teeth biology and in the fine-tuning morphogenesis of craniofacial (lip/palate) and limbs is yet to be outlined prompting future research. We propose refer to these entities (nectin 1-ED and nectin 4-ED) as "nectinopathies", which are likely to be underestimated/underdiagnosed ED syndomes.

Does pre-existing diabetes affect prostate cancer prognosis? A systematic review.

To summarize the influence of pre-existing diabetes on mortality and morbidity in men with prostate cancer. We searched MEDLINE and EMBASE from inception through 1 October 2008. Search terms were related to diabetes, cancer and prognosis. Studies were included if they reported an original data analysis of prostate cancer prognosis, compared outcomes between men with and without diabetes and were in English. Titles, abstracts and articles were reviewed independently by two authors. Conflicts were settled by consensus or third review. We abstracted data on study design, analytic methods, outcomes and quality. We summarized mortality and morbidity outcomes qualitatively and conducted a preliminary meta-analysis to quantify the risk of long-term (>3 months), overall mortality. In total, 11 articles were included in the review. Overall, one of four studies found increased prostate cancer mortality, one of two studies found increased nonprostate cancer mortality and one study found increased 30-day mortality. Data from four studies could be included in a preliminary meta-analysis for long-term, overall mortality and produced a pooled hazard ratio of 1.57 (95% CI: 1.12-2.20). Diabetes was also associated with receiving radiation therapy, complication rates, recurrence and treatment failure. Our analysis suggests that pre-existing diabetes affects the treatment and outcomes of men with prostate cancer.

Joubert syndrome with bilateral polymicrogyria: clinical and neuropathological findings in two brothers.

Joubert syndrome (JS) is characterized by hypotonia, ataxia, developmental delay, and a typical neuroimaging finding, the so-called "molar tooth sign" (MTS). The association of MTS and polymicrogyria (PMG) has been reported as a distinct JS-related disorder (JSRD). So far, five patients have been reported with this phenotype, only two of them being siblings. We report on one additional family, describing a living child with JS and PMG, and the corresponding neuropathological picture in the aborted brother. No mutations were detected in the AHI1 gene, the only so far associated with the JS + PMG phenotype. Moreover, linkage analysis allowed excluding all known gene loci, suggesting further genetic heterogeneity.

Postchallenge hyperglycemia and mortality in a national sample of U.S. adults.

OBJECTIVE: Although postchallenge hyperglycemia is a well-established feature of type 2 diabetes, its association with risk of mortality is uncertain. Therefore, the aim of this study was to assess the independent association of fasting and 2-h glucose levels with all-cause and cardiovascular disease (CVD) mortality. RESEARCH DESIGN AND METHODS: We analyzed data from the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study, a prospective cohort study of U.S. adults examined in the NHANES II, and focused on the 3,092 adults aged 30-74 years who underwent an oral glucose tolerance test at baseline (1976-1980). Deaths were identified from U.S. national mortality files from 1976 to 1992. To account for the complex survey design, we used SUDAAN statistical software for weighted analysis. RESULTS: Compared with their normoglycemic counterparts (fasting glucose [FG] < 7.0 and 2-h glucose < 7.8 mmol/l), adults with fasting and postchallenge hyperglycemia (FG > or =7.0 and 2-h glucose > or =11.1 mmol/l) had a twofold higher risk of death after 16 years of follow-up (age- and sex-adjusted relative hazard [RH] 2.1, 95% CI 1.4-3.2). However, adults with isolated postchallenge hyperglycemia (FG < 7.0 and 2-h glucose > or =11.1 mmol/l) were also at higher risk of death (1.6, 1.0-2.6). In proportional hazards analysis, FG (fully adjusted RH 1.10 per 1 SD; 95% CI 1.01, 1.22) and 2-h glucose (1.14, 1.00-1.29) showed nearly identical predictive value for mortality. Similar trends were observed for CVD mortality. CONCLUSIONS: These results suggest that postchallenge hyperglycemia is associated with increased risk of all-cause and CVD mortality independently of other CVD risk factors.

Diabetes and the risk of infection-related mortality in the U.S.

OBJECTIVE: To determine whether diabetes predicts infection-related mortality and to clarify the extent to which this relationship is mediated by comorbid conditions that may themselves increase risk of infection. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study using the Second National Health and Nutrition Examination Survey Mortality Study of 9,208 adults aged 30-74 years in 1976-1980. We defined demographic variables, diabetes, cardiovascular disease (CVD), and smoking by self-report; BMI, blood pressure, and serum cholesterol from baseline examination; and cause-specific mortality from death certificates. RESULTS: Over 12-16 years of follow-up, 36 infection-related deaths occurred among 533 adults with diabetes vs. 265 deaths in 8,675 adults without diabetes (4.7 vs. 1.5 per 1,000 person-years, P < 0.001). Diabetes (RR 2.0, 95% CI 1.2-3.2) and congestive heart failure (2.8, 1.6-5.1) were independent predictors of infection-related mortality after simultaneous adjustment for age, sex, race, poverty status, smoking, BMI, and hypertension. After subdividing infection-related deaths into those with (n = 145) and without (n = 156) concurrent cardiovascular diagnoses at the time of death, diabetic adults were at risk for infection-related death with CVD (3.0, 1.8-5.0) but not without CVD (1.0, 0.5-2.2). CONCLUSIONS: These nationally representative data suggest that diabetic adults are at greater risk for infection-related mortality, and the excess risk may be mediated by CVD.

Subclinical states of glucose intolerance and risk of death in the U.S.

OBJECTIVE: Although clinically evident type 2 diabetes is a well-established cause of mortality, less is known about subclinical states of glucose intolerance. RESEARCH DESIGN AND METHODS: Data from the Second National Health and Nutrition Examination Survey Mortality Study, a prospective study of adults, were analyzed. This analysis focused on a nationally representative sample of 3,174 adults aged 30-75 years who underwent an oral glucose tolerance test at baseline (1976-1980) and who were followed up for death through 1992. RESULTS: Using 1985 World Health Organization criteria, adults were classified as having previously diagnosed diabetes (n = 248), undiagnosed diabetes (n = 183), impaired glucose tolerance (IGT) (n = 480), or normal glucose tolerance (n = 2,263). For these groups, cumulative all-cause mortality through age 70 was 41, 34, 27, and 20%, respectively (P < 0.001). Compared with those with normal glucose tolerance, the multivariate adjusted RR of all-cause mortality was greatest for adults with diagnosed diabetes (RR 2.11, 95% CI 1.56-2.84), followed by those with undiagnosed diabetes (1.77, 1.13-2.75) and those with IGT (1.42, 1.08-1.87; P < 0.001). A similar pattern of risk was observed for cardiovascular disease mortality. CONCLUSIONS: In the U.S., there was a gradient of mortality associated with abnormal glucose tolerance ranging from a 40% greater risk in adults with IGT to a 110% greater risk in adults with clinically evident diabetes. These associations were independent of established cardiovascular disease risk factors.

Age 85+ years accelerates large-fiber peripheral nerve dysfunction and diabetes contributes even in the oldest-old: the Women's Health and Aging Study.

BACKGROUND: Both diabetes mellitus and advancing age are associated with peripheral nerve dysfunction (PND). However, the independent and potentially synergistic effects of these factors in old age are poorly described, especially among the oldest-old and among people with an existing disability. METHODS: A total of 894 women aged 65+ years participating in the Women's Health and Aging Study received a baseline home interview and clinical examination during which PND was evaluated by the Vibratron II. Age and diabetes were examined in relation to the level of PND (normal, mild, moderate, or severe). Height, alcohol consumption, smoking, report of neurologic symptoms, and diabetes duration were examined as potential confounders. RESULTS: Eighteen percent of the sample reported diabetes, 42% had normal nerve function, and 23.9%, 14.5%, and 19.5% had mild, moderate, and severe PND, respectively. Women aged 85+ years had 6.5, 7.5, and 13.3 times the odds of mild, moderate, and severe PND relative to women aged 65-74 years, adjusted for diabetes and height. Women who reported diabetes had 1.8, 2.4, and 1.6 times the risk of mild, moderate, and severe PND relative to those who did not, adjusted for age and height. No interaction between age and diabetes was observed. CONCLUSIONS: Age is strongly associated with decrements in large-fiber peripheral nerve function in disabled women aged 65+ years, with greatly accelerated risk among those aged 85+ years. Despite the overwhelmingly strong effects of advancing age on PND in this cohort, diabetes remains a significant correlate of PND. Future studies may determine whether prevention or control of diabetes is effective in reducing the occurrence of PND in old age and whether a reduction in PND will translate into reduced disability in this age group.

Nontraditional risk factors for coronary heart disease incidence among persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Major risk factors explain much of the excess risk for coronary heart disease produced by diabetes, but nontraditional factors may also relate to incident coronary heart disease. OBJECTIVE: To examine the association of traditional and nontraditional risk factors with incidence of coronary heart disease in adults with diabetes. DESIGN: Prospective cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) Study. PARTICIPANTS: 1676 middle-aged persons who had diabetes but no history of prevalent coronary heart disease. MEASUREMENTS: Multiple risk factors were recorded at baseline. Follow-up was from 1987 through 1995. RESULTS: 186 participants developed incident coronary heart disease events during follow-up. As expected, the incidence of coronary heart disease in participants with diabetes was associated positively with traditional risk factors (hypertension, smoking, total cholesterol level, and low high-density lipoprotein [HDL] cholesterol level). After adjustment for sex, age, ethnicity, and ARIC field center, incident coronary heart disease was also significantly associated with waist-to-hip ratio; levels of HDL3 cholesterol, apolipoproteins A-I and B, albumin, fibrinogen, and von Willebrand factor factor VIII activity; and leukocyte count. However, after adjustment for traditional risk factors for coronary heart disease, only levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count remained independently associated with coronary heart disease (P < 0.03). The relative risks associated with the highest compared with lowest groupings of albumin, fibrinogen, factor VIII, and von Willebrand factor values and leukocyte count were 0.64 (95% CI, 0.44 to 0.92), 1.75 (CI, 1.12 to 2.73), 1.58 (CI, 1.02 to 2.42), 1.71 (CI, 1.11 to 2.63), and 1.90 (CI, 1.16 to 3.13), respectively. Adjustment for diabetes treatment status attenuated these associations somewhat. CONCLUSIONS: Levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count were predictors of coronary heart disease among persons with diabetes. These associations may reflect 1) the underlying inflammatory reaction or microvascular injury related to atherosclerosis and a tendency toward thrombosis or 2) common antecedents for both diabetes and coronary heart disease.

Depressive symptoms and metabolic control in African-Americans with type 2 diabetes.

OBJECTIVE: To determine the prevalence of depressive symptoms and the relationship between depressive symptoms and metabolic control. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 183 African-American adults aged 35-75 years with type 2 diabetes who were recruited from two primary care clinics in East Baltimore, Maryland. Depressive symptoms, using the Center for Epidemiological Studies Depression Scale (CES-D), HbA1c, fasting lipid profile, BMI, and blood pressure, were measured on each participant. Diabetes-related health behaviors were assessed by questionnaire. RESULTS: The prevalence of depressive symptoms (CES-D > or =22) was 30%. After adjustment for age, sex, income, social support, and duration of diabetes in linear regression models, there were significant graded relationships between greater depressive symptoms and higher serum levels of cholesterol and triglycerides (P<0.050). Similar, albeit less statistically significant, relationships were found with higher levels of HbA1c (P = 0.104), diastolic blood pressure (P = 0.073), and LDL cholesterol (P = 0.176). Unexpectedly, individuals who reported more depressive symptoms also had higher serum levels of HDL cholesterol (P = 0.047). The associations were not explained by differences in diabetes-related health behaviors. CONCLUSIONS: Depressive symptoms are marginally associated with suboptimal levels of HbA1c, diastolic blood pressure, and LDL cholesterol, and significantly associated with suboptimal levels of total cholesterol and triglyceride levels. Prospective studies are required to determine whether improved identification and management of depressive symptoms would enhance metabolic control in this population.

Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes.

OBJECTIVE: Although hyperglycemia is hypothesized to increase the short-term risk of infection, this hypothesis has not been well tested in a clinical setting. This study was designed to assess the relationship of perioperative glycemic control to the subsequent risk of infectious complications. RESEARCH DESIGN AND METHODS: A total of 411 adults with diabetes who underwent coronary artery surgery from 1990 to 1995 in the cardiac surgery service of an urban university hospital were included in a nonconcurrent prospective cohort study based on chart review. Perioperative glycemic control was characterized by the mean of six capillary glucose measurements taken during the 36-h interval following surgery. The major outcomes studied were infections of leg and chest wounds, pneumonia, and urinary tract infections. RESULTS: Mean postoperative glucose levels ranged from 121 to 352 mg/dl and were divided into quartiles: quartile 1 (121-206 mg/dl), quartile 2 (207-229 mg/dl), quartile 3 (230-252 mg/dl), and quartile 4 (253352 mg/dl). After simultaneous adjustment for age, sex, race, underlying comorbidity, acute severity of illness, and the length of the stay in the surgical intensive care unit, patients with higher mean capillary glucose readings were at increased risk of developing infections. Compared with people in the lowest quartile of postoperative glucose, those in quartiles 2 (relative odds of infection [95% CI] = 1.17 [0.57-2.40]), 3 (1.86 [0.94-3.68]), and 4 (1.78 [0.86-3.47]) were at progressively higher risk for infection (P = 0.05 for trend). CONCLUSIONS: In patients with diabetes who undergo coronary artery surgery, postoperative hyperglycemia is an independent predictor of short-term infectious complications. Physicians should consider a glucose concentration target of < or =200 mg/dl to reduce the risk of infection.

A community-based study of explanatory factors for the excess risk for early renal function decline in blacks vs whites with diabetes: the Atherosclerosis Risk in Communities study.

CONTEXT: The explanation for the excess risk for diabetic renal disease in blacks is uncertain. OBJECTIVES: To compare the incidence of early renal function decline in black and white adults with diabetes and to examine possible explanatory factors for racial differences. DESIGN: Prospective cohort study. SETTING: Four US communities participating in the Atherosclerosis Risk in Communities study. PARTICIPANTS: Community-based sample of 1434 diabetic adults aged 45 to 64 years. MEASUREMENTS: Detailed baseline assessment using structured interview, results of physical examination, and laboratory measurements. MAIN OUTCOME: Development of early renal function decline defined by an increase in serum creatinine of at least 35.4 micromol/L (0.4 mg/dL) during 3 years of follow-up. RESULTS: During 3 years of follow-up, early renal function decline developed in 45 blacks (28.4 per 1000 person-years [PY]) and 25 whites (9.6 per 1000 PY). After adjustment for age, sex, and baseline serum creatinine level, early renal function decline was more than 3 times as likely to develop in blacks than whites (odds ratio, 3.15; 95% confidence interval, 1.86-5.33). Additional adjustment for education, household income, health insurance, fasting glucose level, mean systolic blood pressure, smoking history, and physical activity level reduced the relative odds in blacks to 1.38 (95% confidence interval, 0.71-2.69), corresponding to a 82% reduction in excess risk. CONCLUSIONS: These data suggest that early renal function decline is 3 times more likely to develop in blacks than whites and that potentially modifiable factors, including lower socioeconomic status, suboptimal health behaviors, and suboptimal control of glucose level and blood pressure, account for more than 80% of this disparity.

Body weight patterns from 20 to 49 years of age and subsequent risk for diabetes mellitus: the Johns Hopkins Precursors Study.

BACKGROUND: Obesity in middle age is a well-known risk factor for the development of type 2 diabetes mellitus. However, the importance of weight and weight gain at younger ages is less certain. OBJECTIVE: To determine the relationship of body weight patterns from 20 to 49 years of age with the subsequent risk for type 2 diabetes mellitus. SETTING: An ongoing longitudinal study of former medical students. PARTICIPANTS: Nine hundred sixteen white men without diabetes at 50 years of age. MEASUREMENTS: Weight and height measured in medical school, then assessed by mailed questionnaire to 49 years of age. MAIN OUTCOME: Incident type 2 diabetes mellitus based on physician self-report. RESULTS: During 14 255 person-years of follow-up, there were 35 incident cases of type 2 diabetes mellitus (2.5 per 1000 person-years). After simultaneous adjustment for age, physical activity, lifetime maternal history of diabetes, and smoking, body mass indexes (BMIs; calculated as weight in kilograms divided by the square of height in meters) at 25, 35, and 45 years of age were all strongly associated with diabetes risk (relative risks for overweight [BMI> or =25.0] vs. not overweight, >3.0; all Ps<.05), as were maximum and average BMI to 49 years of age. The relationship of BMI at 25 years of age to diabetes risk was substantially attenuated by adjustment for BMI at 45 years of age and average BMI, but was independent of weight change, weight variability, or maximum BMI. CONCLUSION: In men, overweight at 25 years of age strongly predicts diabetes risk in middle age, largely through its association with overweight at 45 years of age and high average BMI to 49 years of age.

Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Hypomagnesemia has been hypothesized to play a role in coronary heart disease (CHD), but few prospective epidemiologic studies have been conducted. METHODS AND RESULTS: We examined the relation of serum and dietary magnesium with CHD incidence in a sample of middle-aged adults (n=13,922 free of baseline CHD) from 4 US communities. Over 4 to 7 years of follow-up, 223 men and 96 women had CHD develop. After adjustment for sociodemographic characteristics, waist/hip ratio, smoking, alcohol consumption, sports participation, use of diuretics, fibrinogen, total and high-density lipoprotein cholesterol levels, triglyceride levels, and hormone replacement therapy, the relative risk of CHD across quartiles of serum magnesium was 1.00, 0.92, 0.48, and 0.44 (P for trend=0.009) among women and 1.00, 1.32, 0.95, and 0.73 (P for trend=0.07) among men. The adjusted relative risk of CHD for the highest versus the lowest quartile of dietary magnesium was 0.69 in men (95% confidence interval 0.45 to 1.05) and 1.32 in women (0.68 to 2.55). CONCLUSIONS: These findings suggest that low magnesium concentration may contribute to the pathogenesis of coronary atherosclerosis or acute thrombosis.