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.

Modifying diet and exercise in multiple sclerosis (MoDEMS): A randomized controlled trial for behavioral weight loss in adults with multiple sclerosis and obesity.

BACKGROUND: Obesity is a risk factor for developing multiple sclerosis (MS) and MS-related disability. The efficacy of behavioral weight loss interventions among people with MS (pwMS) remains largely unknown. OBJECTIVE: Examine whether a group-based telehealth weight loss intervention produces clinically significant weight loss in pwMS and obesity. METHODS: Seventy-one pwMS were randomized to the weight loss intervention or treatment-as-usual (TAU). The 6-month program promoted established guidelines for calorie reduction and increased physical activity. Anthropometric measurements, mobility tasks, self-report questionnaires, and accelerometry were used to assess changes at follow-up. RESULTS: Mean percent weight loss in the treatment group was 8.6% compared to 0.7% in the TAU group (p < .001). Sixty-five percent of participants in the intervention achieved clinically meaningful weight loss (⩾ 5%). Participants in the treatment group engaged in 46.2 minutes/week more moderate-to-vigorous physical activity than TAU participants (p = .017) and showed improvements in quality of life (p = .012). Weight loss was associated with improved mobility (p = .003) and reduced fatiguability (p = .008). CONCLUSION: Findings demonstrate the efficacy of a behavioral intervention for pwMS and obesity, with clinically significant weight loss for two-thirds of participants in the treatment condition. Weight loss may also lead to improved mobility and quality of life.

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.

Changes in Depressive Symptoms, Perceived Stress, and Food Security Among Study Participants With Metabolic Syndrome During a COVID-19-Mandated Research Pause.

INTRODUCTION: We explored how depressive symptoms, perceived stress, and food security of people with metabolic syndrome (MetS) changed during the COVID-19 pandemic. METHODS: An online survey was administered from October 2019 through March 2020, to participants in a 2-year lifestyle intervention trial to reverse MetS; the survey was repeated during the COVID-19 pandemic. Outcomes were a change in depressive symptoms, perceived stress, and food security as measured by the Patient Health Questionnaire-8 (PHQ-8), Perceived Stress Scale, and US Department of Agriculture's 10-item Adult Food Security Module. We analyzed changes in outcomes with measures of association, paired t tests, repeated measures, and independent t tests. RESULTS: Survey respondents (N = 132) were mostly female (67%), White (70%), and middle-aged, with a median income of $86,000. Frequency of depressive symptoms increased from baseline to follow-up and the increase was related to lower mean (SD) baseline vitality (44.4 [20.7] vs 60.3 [18.9]; P = .01) and mental health decline (71.0 [14.3] vs 82.0 [10.4]; P = .002). Mean (SD) perceived stress was significantly higher at baseline than follow-up (18.5 [6.4] vs 14.9 [7.2]; P < .001). Food security increased from 83% at baseline to 90% at follow-up (P < .001). Movement to or continued food insecurity (n = 13) tended to be associated with a racial or ethnic minority group (P = .05). CONCLUSION: A sample at high risk for COVID-19 did not experience increased stress or food insecurity, but demonstrated increased depressive symptoms after the onset of the COVID-19 pandemic, with some baseline susceptibility.

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.

A Case-Based Comparison of the American Thyroid Association and Thyroid Imaging Reporting & Data System Guidelines.

Thyroid nodules are a common clinical finding. Approximately 4-7% of the population have a palpable nodule on physical exam,1 while up to 70% of the population have a nodule detected incidentally on ultrasound.2 The vast majority of nodules are benign, however, approximately 5-13% of thyroid nodules detected on imaging are at risk of malignancy.3 Some malignant nodules, especially those smaller than 1 cm, can exhibit indolent behavior and do not require aggressive treatment.4 Therefore, thyroid nodules need to be accurately assessed to avoid overdiagnosis and overtreatment of nodules which would not otherwise affect patient morbidity. The American Thyroid Association (ATA) addressed this challenge by developing a set of ultrasound pattern-based guidelines for thyroid nodule management in 2009, which were updated in 2015.5 Other societies have since published similar guidelines, such as the Thyroid Imaging Reporting & Data System (TI-RADS) by the American College of Radiology in 2017. TI-RADS was similarly intended to risk-stratify nodules based on ultrasound appearance, but uses a points-based approach. The purpose of this review is to provide an overview of thyroid nodule evaluation and management through a case-based comparison using the ATA and TI-RADS guidelines.

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.

The Role of the Fracture Liaison Service in Osteoporosis Care.

Osteoporosis is a disease classified by the alteration of bony microarchitecture predisposing a person to fragility fractures. This costs the US $19 billion per year and is expected to rise as our population ages. Only 20% of patients with fragility fractures receive treatment for osteoporosis. A Fracture Liaison Service is a cost-effective way to follow patients and improve appropriate work up and management from multiple medical disciplines.

Late Onset Hypercalcemia in an HIV Patient as a Manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS).

Hypercalcemia in human immunodeficiency virus (HIV) patients can be challenging due to various underlying mechanisms. 1,25- dihydroxycholecalciferol (1,25 (OH)2 vitamin D)-mediated hypercalcemia due to increased activity of extrarenal 1-alpha hydroxylase is one of the well-known mechanisms of hypercalcemia described in HIV patients. Mycobacterium avium-intracellulare (MAI) is a granulomatous disease that can cause hypercalcemia due to ectopic production of alpha -1 hydroxylase and result in increased levels of 1,25 (OH)2 vitamin D. Herein, we present a case of "late-onset" hypercalcemia in a patient with HIV/AIDS and MAI infection in the setting of suspected immune reconstitution inflammatory syndrome (IRIS). The hypercalcemia workup showed an inappropriately average level of 1,25 (OH)2 vitamin D while the rest of the workup was unrevealing. Unusually normal levels of vitamin D metabolites were the driving mechanism of hypercalcemia in this case. The late presentation of hypercalcemia was likely due to IRIS unmasking an underlying granulomatous infection, and this consideration led to the successful treatment of the patient with steroid administration. This case emphasizes the importance of considering IRIS in evaluating hypercalcemia that presents late in the course of granulomatous infections in HIV patients.

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.

Association between frailty and sleep quality in people living with multiple sclerosis and obesity: An observational cross-sectional study.

BACKGROUND: A majority of the people with multiple sclerosis (pwMS) experience sleep disturbances. Frailty is also common in pwMS. The geriatric literature strongly suggests that frailty is associated with worse sleep outcomes in community-dwelling older adults, but this association has yet to be explored among pwMS. This study focused on examining the association between frailty and sleep quality in pwMS. METHODS: Seventy-six people with both MS and obesity (mean age: 47.6 ± 10.9 years, 81.6 % female, mean body mass index (BMI): 37.10 ± 5.5 kg/m2, mean Patient Determined Disease Steps (PDDS): 0.82 ± 1.20) were included in this cross-sectional secondary analysis. A comprehensive frailty index (FI) based on 41 health deficits from various health domains was calculated based on standardized procedures. Sleep quality was determined by the Pittsburgh Sleep Quality Index questionnaire (PSQI). RESULTS: Overall, 67.1 % of the participants were identified as non-frail (FI ≤ 0.25), and 32.9 % were identified as frail (FI > 0.25). A significant correlation was observed between FI scores and global PSQI scores (ρ = 0.43, p < 0.05). Cross-tabulation analyses revealed that frail participants had worse subjective sleep quality, sleep latency, habitual sleep efficiency, sleep disturbances, daytime dysfunction, and higher use of sleep medications compared to non-frail participants (p < 0.05). CONCLUSIONS: The current study identified a significant association between frailty and sleep quality in people with both MS and obesity with minimal disability. These findings underscore the importance of untangling the relationship between frailty and sleep quality in pwMS. These results could lead to a more targeted approach for rehabilitation interventions aiming to improve frailty in MS.

Genome-wide association study identifies ALDH7A1 as a novel susceptibility gene for osteoporosis.

Osteoporosis is a major public health problem. It is mainly characterized by low bone mineral density (BMD) and/or low-trauma osteoporotic fractures (OF), both of which have strong genetic determination. The specific genes influencing these phenotypic traits, however, are largely unknown. Using the Affymetrix 500K array set, we performed a case-control genome-wide association study (GWAS) in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls). A follow-up replication study was conducted to validate our major GWAS findings in an independent Chinese sample containing 390 cases with hip OF and 516 controls. We found that a SNP, rs13182402 within the ALDH7A1 gene on chromosome 5q31, was strongly associated with OF with evidence combined GWAS and replication studies (P = 2.08x10(-9), odds ratio = 2.25). In order to explore the target risk factors and potential mechanism underlying hip OF risk, we further examined this candidate SNP's relevance to hip BMD both in Chinese and Caucasian populations involving 9,962 additional subjects. This SNP was confirmed as consistently associated with hip BMD even across ethnic boundaries, in both Chinese and Caucasians (combined P = 6.39x10(-6)), further attesting to its potential effect on osteoporosis. ALDH7A1 degrades and detoxifies acetaldehyde, which inhibits osteoblast proliferation and results in decreased bone formation. Our findings may provide new insights into the pathogenesis of osteoporosis.

Thyrotoxic Periodic Paralysis as an Ongoing Diagnostic Challenge: A Case Report and Literature Review.

Thyrotoxic periodic paralysis (TPP) is a rare condition that presents with episodic periodic paralysis due to hypokalemia that develops from hyperthyroidism. Timely diagnosis is still an ongoing challenge due to lack of awareness, self-resolving episodes, and the fact that it clinically mimics familial hypokalemic periodic paralysis (FHPP), which is more common in the West. TPP is more commonly seen among Asians but has been emerging in Western countries due to globalization. We present a case of a 24-year-old Hispanic male who presented with bilateral lower extremity weakness. He had five such episodes in the past year, which resolved on their own. The current episode of weakness was worse, and he required a wheelchair to ambulate. Despite extensive work, it took over four months to make a definitive diagnosis and treat his hyperthyroidism. A literature review reported that most cases of TPP are usually diagnosed after multiple episodes, and the causes of diagnostic error were studied. Through this review, we present a case of TPP with diagnostic delay, a literature review discussing the etiology, pathogenesis, clinical manifestations, and management, with an emphasis on the diagnostic challenge of TPP. Awareness of this condition, timely evaluation for hyperthyroidism as a cause for hypokalemic periodic paralysis, and understanding the factors that contribute to its diagnostic challenge will aid in timely recognition and treatment.

Hypercalcemia Secondary to Antibiotic-Eluting Calcium Sulfate Beads.

The use of calcium sulfate beads (CSBs) as a carrier for local delivery of antibiotics is increasingly reported for the treatment of localized infections. They are used most commonly in bone and joint infections, post-trauma infections, diabetes-related foot wounds, and vascular grafts. Hypercalcemia is rarely reported with CSB use but is an important safety concern, and patients at higher risk should be identified prospectively and followed carefully postoperatively. This case report details an 85-year-old male who developed severe, symptomatic postoperative hypercalcemia after antibiotic bead placement in the right knee. He presented with confusion, weakness, and lethargy, and was subsequently treated with fluids, calcitonin, and alendronate. The patient quickly returned to normal mental status, and calcium levels normalized, leading to discharge. The case report and review of the literature describe an incident of severe hypercalcemia attributed to the use of antibiotic-eluting CSBs and describe the risk factors and time course that may be expected.

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.