Gestational Diabetes Mellitus and Metabolic Syndrome: A Review of the Associations and Recommendations.

OBJECTIVE: Gestational diabetes mellitus (GDM) and metabolic syndrome (MetS) share common characteristics and risk factors. Both conditions increase the risk of chronic diseases and, thus, may share a common pathogenesis. This review begins with a clinical vignette, followed by evidence supporting the risk of MetS after GDM among women and their offspring and the risk of having GDM among pregnant women who have MetS before pregnancy. METHODS: Research studies published between 2010 and 2023 were identified via several databases, including PubMed, the Web of Science, MEDLINE, Science Direct, ERIC, and EBSCOhost. Search terms included gestational diabetes and metabolic syndrome. Reviews, books/e-books, patents, news, trade publications, reports, dissertations/theses, conference materials, and articles in non-English languages were all excluded. RESULTS: MetS increases not only the incidence of GDM during pregnancy but also the risk of diabetes in women with a history of GDM. On the other hand, women with a history of GDM had an almost 4 times increased risk of developing MetS at minimum of 1 year after delivery, and the risk increases with longer time lapse since the index pregnancy. Prepregnancy body mass index appears to be the strongest factor predicting MetS. Children exposed to GDM in utero have at least a 2 times increased risk of MetS in later life. CONCLUSION: Timely assessment and continuing surveillance of MetS before and after pregnancy followed by GDM are recommended. Weight management and nutrition counseling are of importance to reduce the risk of GDM and MetS among pregnant women.

Examination of eating competence in a geo-diverse sample with metabolic syndrome.

Eating competence (EatC) is an intra-individual approach to eating attitudes and behaviors associated with greater well-being. EatC research has not included persons with confirmed metabolic syndrome (MetS). Therefore, EatC of persons with MetS was explored to identify unique associations and inform implementation of MetS lifestyle interventions using baseline data from a multisite, randomized trial of a 2-year lifestyle intervention with MetS. EatC, measured with the Satter Eating Competence Inventory 2.0 (ecSI 2.0™), was examined for relationships with bioclinical measures (e.g., blood pressure, lipids), medication use, BMI, waist circumference, fruit/vegetable intake, and psychosocial factors, (e.g., stress, mindfulness). Data were collected in person and video call by trained research personnel. EatC was examined as a continuous score and as a categorical variable with ecSI 2.0™ scores ≥ 32 considered eating competent. Participants (n = 618) were predominantly female (76%), White (74%), college educated (60%). Mean age was 55.5 ± 11 y. Mean ecSI 2.0™ was 29.9 ± 7.4 and 42% were eating competent. EatC was greater for males, persons who were older and food secure. Competent eaters (vs. non-eating competent) had lower waist circumference (112.7 ± 12.5 cm vs.116.8 ± 16.0 cm; P < 0.001) and BMI (35.0 ± 6.1 vs. 37.5 ± 7.3; P < 0.001). Serum triglycerides, HDL-cholesterol, fasting blood glucose, HbA1c, and blood pressure did not differ by EatC status. Compared to non-eating competent persons, competent eaters perceived less stress, were more mindful, indicated better physical function, and more habitual vegetable intake (all P < 0.001) and sensory awareness (P < 0.05). EatC in MetS paralleled the non-MetS profile. EatC was associated with a healthier psychosocial profile, waist circumference and BMI. Findings support further research to examine the mediational or moderating influence of EatC in the treatment of MetS.

Growth Differentiation Factor 15 (GDF-15), a New Biomarker in Heart Failure Management.

The emergence of biomarkers across medicine's subspecialties continues to evolve. In essence, a biomarker is a biological observation that clearly substitutes a clinical endpoint or intermediate outcome not only are more difficult to observe but also, biomarkers are easier, less expensive and could be measured over shorter periods. In general, biomarkers are versatile and not only used for disease screening and diagnosis but, most importantly, for disease characterization, monitoring, and determination of prognosis as well as individualized therapeutic responses. Obviously, heart failure (HF) is no exception to the use of biomarkers. Currently, natriuretic peptides are the most used biomarkers for both diagnosis and prognostication, while their role in the monitoring of treatment is still debatable. Although several other new biomarkers are currently under investigation regarding diagnosis and determination of prognosis, none of them are specific for HF, and none are recommended for routine clinical use at present. However, among these emerging biomarkers, we would like to highlight the potential for growth differentiation factor (GDF)-15 as a plausible new biomarker that could be helpful in providing prognostic information regarding HF morbidity and mortality.

Dysregulation of Gene Expression of Key Signaling Mediators in PBMCs from People with Type 2 Diabetes Mellitus.

Diabetes is currently the fifth leading cause of death by disease in the USA. The underlying mechanisms for type 2 Diabetes Mellitus (DM2) and the enhanced susceptibility of such patients to inflammatory disorders and infections remain to be fully defined. We have recently shown that peripheral blood mononuclear cells (PBMCs) from non-diabetic people upregulate expression of inflammatory genes in response to proteasome modulators, such as bacterial lipopolysaccharide (LPS) and soybean lectin (LEC); in contrast, resveratrol (RES) downregulates this response. We hypothesized that LPS and LEC will also elicit a similar upregulation of gene expression of key signaling mediators in (PBMCs) from people with type 2 diabetes (PwD2, with chronic inflammation) ex vivo. Unexpectedly, using next generation sequencing (NGS), we show for the first time, that PBMCs from PwD2 failed to elicit a robust LPS- and LEC-induced gene expression of proteasome subunit LMP7 (PSMB8) and mediators of T cell signaling that were observed in non-diabetic controls. These repressed genes included: PSMB8, PSMB9, interferon-γ, interferon-λ, signal-transducer-and-activator-of-transcription-1 (STAT1), human leukocyte antigen (HLA DQB1, HLA DQA1) molecules, interleukin 12A, tumor necrosis factor-α, transporter associated with antigen processing 1 (TAP1), and several others, which showed a markedly weak upregulation with toxins in PBMCs from PwD2, as compared to those from non-diabetics. Resveratrol (proteasome inhibitor) further downregulated the gene expression of these inflammatory mediators in PBMCs from PwD2. These results might explain why PwD2 may be susceptible to infectious disease. LPS and toxins may be leading to inflammation, insulin resistance, and thus, metabolic changes in the host cells.

Food and Nutrition Security in Clinical Settings.

Food insecurity affects fourteen million American households. Due to the impact on health outcomes and costs of care, food insecurity is one of the leading health and nutrition issues in the U.S. In this article, we provide an overview of food and nutrition insecurity and how it is measured, followed by health consequences of food insecurity, and then discuss ways that physicians and health professionals can help address food and nutrition security in clinical setting.

Childhood Obesity in the State of Missouri: A Review for Providers to Counsel and Treat Patients.

Childhood obesity is a common disease both nationally and in the state of Missouri. Obesity in childhood is often under-recognized and is difficult to treat. Screening, accurate diagnosis, and counseling is imperative to proper management. Common barriers to treatment include a lack of accurate identification and a lack of awareness of needed and available treatments of this disease in the pediatric setting. This review article highlights behavioral measures as well as pharmacologic and surgical therapies for obesity in children. This review is intended as guidance for providers to properly counsel and treat patients with this disease.

A culturally and linguistically adapted text-message Diabetes Prevention Program for Latinos: Feasibility, acceptability, and preliminary effectiveness.

Despite the general positive outcomes of the Diabetes Prevention Program (DPP), the program's reach, adherence, and effectiveness among Latinos are still suboptimal. Text-message DPP can potentially overcome barriers and improve DPP outcomes for this group. We aimed to assess the feasibility, acceptability, and preliminarily effectiveness of a culturally and linguistically adapted text-message DPP for Latinos. We enrolled 26 eligible Spanish-speaking Latino adults at risk of developing type 2 diabetes (A1c = 5.7%-6.4%, body mass index ≥25) in a 6-month culturally and linguistically adapted text-message DPP. Participants received (i) two to three daily automated text-messages about healthy eating, physical activity, problem-solving skills, lifestyle change motivation, and logistics, (ii) on-demand keyword-driven messages, and (iii) on-demand chat messages with a DPP coach. Outcomes included feasibility (e.g. adherence), acceptability (e.g. satisfaction), and preliminary effectiveness (e.g. weight loss). Twenty-four participants completed the program and follow-up assessments. Participants' mean body weight changed from 191.2 to 186.7 pounds (P = .004); 45.8% of participants lost ≥3%, and 29.2% lost ≥5% of body weight. Body mass index and waist circumference were also reduced [0.9 kg/m2 (P = .003) and 1.1 cm (P = .03), pre-post]. Self-reported physical activity frequency was increased (P = .003). No statistically significant changes in diet quality were found. Most participants were satisfied with the program and perceived it to help prevent diabetes. Our pilot study of an innovative text-message DPP for Latinos demonstrated the program was acceptable, feasible, and potentially effective. Using text-message for DPP can reduce barriers to in-person participation by increasing the program's reach without compromising fidelity and effectiveness.

The Diabetes Prevention Program (DPP) is an in-person program that helps people to reduce their risk of having diabetes by supporting them to improve their lifestyles. However, the program is not working well for Latinos. It is possible that offering the program using text-messages for Latinos can support them in improving their lifestyles so they can reduce their chances of getting diabetes. We developed a text-message DPP for Latinos who speak Spanish to test if the program would work for them. A total of 26 Latinos received 2 to 3 daily text-messages about healthy eating, physical activity, and motivations to change lifestyles, for a period of 6 months. Participants also had the chance to send messages to coaches to get individualized responses. By the end of the 6 months, 24 Latinos completed the program. Participants reduced an average of 5.5 pounds in body weight. We also saw reductions in participants' waist circumferences. In addition, participants started to do more physical activity. Most participants were satisfied with the program and perceived it helped them prevent diabetes. In conclusion, we believe that our program worked well and was successful in helping Latinos to change their lifestyles to prevent diabetes.

Hypocalcemia and Hypoparathyroidism Associated With Critical Illness and Aplastic Anemia.

Background/Objective: Severe hypocalcemia is common in critically ill patients. There are different mechanisms. To our knowledge, there are no data about the acute presentation of hypocalcemia at the time of diagnosis of aplastic anemia (AA). The objective of this case report was to describe the case of hypoparathyroidism with severe hypocalcemia in a critically ill patient with AA. Case Report: A 60-year-old man presented with severe hypocalcemia with a calcium level of 6.1 mg/dL (reference range, 8.6-10.3 mg/dL) and hypoparathyroidism with a parathyroid hormone level of 11 pg/mL (reference range, 12-88 pg/mL). He developed a critical state caused by newly diagnosed AA and its complications, such as an acute decrease in the platelet value to a critically low level of 2 × 103/cmm, complicated by neutropenic fever and lower gastrointestinal bleeding. After the initiation of immunosuppressive therapy for AA, his parathyroid hormone-calcium metabolism improved and remained stable but did not normalize completely. Discussion: In our patient, hypoparathyroidism with hypocalcemia may have been caused by cytokine-related upregulation of the calcium-sensing receptor in the setting of AA. On the other hand, given the severity of the initial hypocalcemia and only partial improvement in calcium homeostasis with residual mild hypocalcemia after treatment initiation for AA, autoimmune causes cannot be entirely ruled out, nor could a combination of cytokine-mediated and autoimmune causes. Conclusion: It is essential to treat the underlying causes of hypocalcemia, which, in this case, were AA and hypoparathyroidism.

Prevalence and Risk Factors of Major Depression in Patients with Diabetic Retinopathy in a Nationally Representative Survey.

PURPOSE: Evaluate the prevalence and risk factors of depression in diabetic retinopathy (DR). Compare subjective and objective measures of visual function predictivity of depression. METHODS: National Health and Nutrition Examination Survey 2005-2008 participants aged ≥40 who underwent fundus photography, Patient Health Questionnaire (PHQ)-9, and Visual Function Questionnaire (VFQ-25) were included in the study. Multivariable logistic regression was used to evaluate whether DR was a significant risk factor for depression and to evaluate the risk factors for depression in those with DR. RESULTS: A total of 5704 participants, 47% male, and mean age 56.5 years were included in this study. Persons with moderate, severe non-proliferative diabetic retinopathy (NPDR), or proliferative retinopathy (PDR) had higher prevalence of depression than participants with mild retinopathy or no retinopathy (14.3%, 6.9%, 7.0%). Moderate-to-severe NPDR or PDR (OR: 2.36, p = .04) was associated with depression. Among persons with DR, best-corrected visual acuity and HbA1c were not associated with depression. However, self-reported measures of vision were associated with depression: some of the time spent worrying about eyesight (OR: 4.59, p = .010), vision limit activities some of the time (OR: 8.52, p < .001), vision limits activities most/all of the time (OR: 6.99, p < .001). CONCLUSIONS: A significant proportion of patients with DR in the NHANES population had co-morbid major depression. Best corrected visual acuity was not associated with depression in those with DR, while subjective, self-reported measures were associated with depression, suggesting subjective measures are a better determinant of poor mood and low functional status.

Genome-wide association analyses identify SPOCK as a key novel gene underlying age at menarche.

For females, menarche is a most significant physiological event. Age at menarche (AAM) is a trait with high genetic determination and is associated with major complex diseases in women. However, specific genes for AAM variation are largely unknown. To identify genetic factors underlying AAM variation, a genome-wide association study (GWAS) examining about 380,000 SNPs was conducted in 477 Caucasian women. A follow-up replication study was performed to validate our major GWAS findings using two independent Caucasian cohorts with 854 siblings and 762 unrelated subjects, respectively, and one Chinese cohort of 1,387 unrelated subjects--all females. Our GWAS identified a novel gene, SPOCK (Sparc/Osteonectin, CWCV, and Kazal-like domains proteoglycan), which had seven SNPs associated with AAM with genome-wide false discovery rate (FDR) q<0.05. Six most significant SNPs of the gene were selected for validation in three independent replication cohorts. All of the six SNPs were replicated in at least one cohort. In particular, SNPs rs13357391 and rs1859345 were replicated both within and across different ethnic groups in all three cohorts, with p values of 5.09 x 10(-3) and 4.37 x 10(-3), respectively, in the Chinese cohort and combined p values (obtained by Fisher's method) of 5.19 x 10(-5) and 1.02 x 10(-4), respectively, in all three replication cohorts. Interestingly, SPOCK can inhibit activation of MMP-2 (matrix metalloproteinase-2), a key factor promoting endometrial menstrual breakdown and onset of menstrual bleeding. Our findings, together with the functional relevance, strongly supported that the SPOCK gene underlies variation of AAM.

Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis.

Osteoporosis, a highly heritable disease, is characterized mainly by low bone-mineral density (BMD), poor bone geometry, and/or osteoporotic fractures (OF). Copy-number variation (CNV) has been shown to be associated with complex human diseases. The contribution of CNV to osteoporosis has not been determined yet. We conducted case-control genome-wide CNV analyses, using the Affymetrix 500K Array Set, in 700 elderly Chinese individuals comprising 350 cases with homogeneous hip OF and 350 matched controls. We constructed a genomic map containing 727 CNV regions in Chinese individuals. We found that CNV 4q13.2 was strongly associated with OF (p = 2.0 x 10(-4), Bonferroni-corrected p = 0.02, odds ratio = 1.73). Validation experiments using PCR and electrophoresis, as well as real-time PCR, further identified a deletion variant of UGT2B17 in CNV 4q13.2. Importantly, the association between CNV of UGT2B17 and OF was successfully replicated in an independent Chinese sample containing 399 cases with hip OF and 400 controls. We further examined this CNV's relevance to major risk factors for OF (i.e., hip BMD and femoral-neck bone geometry) in both Chinese (689 subjects) and white (1000 subjects) samples and found consistently significant results (p = 5.0 x 10(-4) -0.021). Because UGT2B17 encodes an enzyme catabolizing steroid hormones, we measured the concentrations of serum testosterone and estradiol for 236 young Chinese males and assessed their UGT2B17 copy number. Subjects without UGT2B17 had significantly higher concentrations of testosterone and estradiol. Our findings suggest the important contribution of CNV of UGT2B17 to the pathogenesis of osteoporosis.

Genome-wide association scans identified CTNNBL1 as a novel gene for obesity.

Obesity is a major public health problem with strong genetic determination; however, the genetic factors underlying obesity are largely unknown. In this study, we performed a genome-wide association scan for obesity by examining approximately 500 000 single-nucleotide polymorphisms (SNPs) in a sample of 1000 unrelated US Caucasians. We identified a novel gene, CTNNBL1, which has multiple SNPs associated with body mass index (BMI) and fat mass. The most significant SNP, rs6013029, achieved experiment-wise P-values of 2.69 x 10(-7) for BMI and of 4.99 x 10(-8) for fat mass, respectively. The SNP rs6013029 minor allele T confers an average increase in BMI and fat mass of 2.67 kg/m(2) and 5.96 kg, respectively, compared with the alternative allele G. We further genotyped the five most significant CTNNBL1 SNPs in a French case-control sample comprising 896 class III obese adults (BMI > or = 40 kg/m(2)) and 2916 lean adults (BMI < 25 kg/m(2)). All five SNPs showed consistent associations with obesity (8.83 x 10(-3) < P < 6.96 x 10(-4)). Those subjects who were homozygous for the rs6013029 T allele had 1.42-fold increased odds of obesity compared with those without the T allele. The protein structure of CTNNBL1 is homologous to beta-catenin, a family of proteins containing armadillo repeats, suggesting similar biological functions. beta-Catenin is involved in the Wnt/beta-catenin-signaling pathway which appears to contribute to maintaining the undifferentiated state of pre-adipocytes by inhibiting adipogenic gene expression. Our study hence suggests a novel mechanism for the development of obesity, where CTNNBL1 may play an important role. Our study also provided supportive evidence for previously identified associations between obesity and INSIG2 and PFKP, but not FTO.

High prevalence of comorbid autoimmune diseases in adults with type 1 diabetes from the HealthFacts database.

BACKGROUND: Patients with type 1 diabetes (T1D) are at risk for other autoimmune diseases (ie, polyautoimmunity). The prevalence and risk factors of this phenomenon have been underreported in adults and ethnic minorities, and data are lacking regarding non-endocrine autoimmune diseases. METHODS: Study population data were gathered from HealthFacts, a deidentified patient database compiled from electronic medical records systems in the US. Patients with an International Classification of Diseases diagnosis code specifying T1D were included in the study, whereas those with a diagnosis of type 2 diabetes were excluded. RESULTS: The cross-sectional study cohort comprised 158 865 adults with T1D (mean [±SD] age 51.4 ± 18.9 years, 52.5% female). The most common autoimmune diseases were thyroid disease (20.1%), systemic rheumatic diseases (3.4%), rheumatoid arthritis specifically (2.0%), and gastrointestinal autoimmune diseases (1.4%). Most of the autoimmune diseases were more common in women (eg hypothyroidism, hyperthyroidism, celiac disease, rheumatoid arthritis, lupus, and Sjögren syndrome). Caucasians were more likely than other ethnicities to have an additional autoimmune disease. The prevalence of autoimmune diseases increased with increasing age, significantly in women, such that 38.5% of women over 80 years of age had an additional autoimmune disease, compared with 17.9% of women aged ≤29 years. CONCLUSIONS: Additional autoimmunity represents a significant comorbidity in patients with T1D. Autoimmune diseases are more common in Caucasians and in women, and increase with age. Clinicians treating patients with T1D should be aware of the risk factors for additional autoimmune diseases.

Bivariate genome linkage analysis suggests pleiotropic effects on chromosomes 20p and 3p for body fat mass and lean mass.

Total body fat mass (TBFM) and total body lean mass (TBLM) are the major components of the human body. Although these highly correlated phenotypic traits are frequently used to characterize obesity, the specific shared genetic factors that influence both traits remain largely unknown. Our study was aimed at identifying common quantitative trait loci (QTLs) contributing to both TBFM and TBLM. We performed a whole genome-linkage scan study in a large sample of 3255 subjects from 420 Caucasian pedigrees. Bivariate linkage analysis was carried out in both the entire sample and gender-specific subsamples. Several potentially important genomic regions that may harbour QTLs important for TBFM and TBLM were identified. For example, 20p12-11 achieved a LOD score of 2.04 in the entire sample and, in the male subsample, two genomic regions, 20p12 (LOD=2.08) and 3p26-25 (LOD=1.92), showed suggestive linkage. In addition, two-point linkage analyses for chromosome X showed suggestive linkages on Xp22 in the entire sample (LOD=2.14) and significant linkage on Xp22 in the female subsample (LOD=3.05). Complete pleiotropy was suggested for 20p12 and 3p26-25 in males. Our results suggest that QTLs on chromosomes 20p12, 3p26-25 and Xp22 may jointly influence TBFM and TBLM. Further fine mapping and gene identification studies for these pleiotropic effects are needed.

Chromosome 2q32 may harbor a QTL affecting BMD variation at different skeletal sites.

UNLABELLED: BMDs at different skeletal sites share some common genetic determinants. Using PCA and bivariate linkage analysis, we identified a QTL on chromosome 2q32 with significant pleiotropic effects on BMDs at different skeletal sites. INTRODUCTION: BMDs at the hip, spine, and forearm are genetically correlated, suggesting the existence of quantitative trait loci (QTLs) with concurrent effects on BMDs at these three skeletal sites. Consequently, it is important to identify these QTLs in the human genome and, for those implicated QTLs, it is important to differentiate between pleiotropic effects, caused by a single gene that concurrently effects these traits, and co-incident linkage, caused by multiple, closely linked, genes that independently effect these traits. MATERIALS AND METHODS: For a sample of 451 American white pedigrees made up of 4,498 individuals, we evaluated the correlations between BMDs at the three skeletal sites. We carried out principal component analysis (PCA) for the three correlated traits and obtained a major component, PC1, which accounts for >75% of the co-variation of BMDs at the three sites. We subsequently conducted a whole genome linkage scan for PC1 and performed bivariate linkage analysis for pairs of the three traits (i.e., forearm/spine BMD, hip/forearm BMD, and hip/spine BMD). RESULTS: Chromosome region 2q32, near the marker GATA65C03M, showed strong linkage to PC1 (LOD = 3.35). Subsequent bivariate linkage analysis substantiated linkage at 2q32 for each trait pair (LOD scores were 2.65, 2.42, and 2.13 for forearm/spine BMD, hip/forearm BMD, and hip/spine BMD, respectively). Further analyses rejected the hypothesis of co-incident linkage (p(0)[forearm/spine] = 0.0005, p(0)[hip/forearm] = 0.004, p(0)(hip/spine] = 0.001) but failed to reject the hypothesis of pleiotropy (p(1)[forearm/spine] = 0.35, p(1)[hip/forearm] = 0.07, p(1)[hip/spine] = 0.15). CONCLUSIONS: Our results strongly support the conclusion that chromosome region 2q32 may harbor a QTL with pleiotropic effects on BMDs at different skeletal sites.

The University of Missouri-Kansas City School of Medicine: thirty-five years of experience with a nontraditional approach to medical education.

The University of Missouri-Kansas City (UMKC) School of Medicine is a public medical school that opened in 1971 in response to a need to train more physicians in Missouri. As a six-year, integrated, combined-degree program leading to the baccalaureate and medical degrees, the school offers an innovative, nontraditional approach to medical education. In the past 35 years, UMKC has graduated over 2,400 physicians who are successful according to outcomes measures used at other medical schools. With recent interest in reforming medical education to prepare physicians for a changing world, a review of alternative models may be especially instructive.UMKC's academic plan offers a blueprint for the curriculum plan and governance of the school. The plan is built on four hallmarks: (1) a combined baccalaureate/MD program, (2) early exposure to clinical medicine, (3) small-group learning through the docent system, and (4) a continuing ambulatory care clinic experience for four years. This article catalogs the results of this plan including student, faculty, and graduates' perceptions of and satisfaction with the school's educational approach, students' achievement on licensing examinations and in the residency match, graduates' performance in residency programs, and their subsequent career patterns. The authors also discuss lessons learned and adjustments made in response to local needs in the context of a changing environment in education, health care, and health care delivery while continually improving the school's nontraditional approach to medical education. These include changes in basic and clinical science instruction, student assessment, faculty development, and funding and governance.