Kidney fibrosis is the final common pathway of virtually all chronic kidney diseases (CKDs) and is therefore considered to be a promising therapeutic target for these conditions. However, despite great progress in recent years, no targeted antifibrotic therapies for the kidney have been approved, likely because the complex mechanisms that initiate and drive fibrosis are not yet completely understood

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Telomeres are nucleoprotein structures that comprise repetitive nucleotide sequences bound to specialized proteins at the ends (tails) of chromosomes. Often compared to the plastic tips on shoelaces, telomeres cap the ends of chromosomes to prevent them unravelling or tangling. When a cell divides, it loses base pairs from the ends of its telomeres so that, with ageing, the telomeres become shorter;

Since the discovery in the 1600s of microscopic organisms, scientists have investigated the relationship between our health and the microbes that surround and inhabit us. Nowadays, we acknowledge that some microbes are inherently pathogenic, but also that others live mutualistically on and within our bodies and contribute to maintaining our well-being. Yet, one prominent challenge remains: to convincingly

OBJECTIVE To examine whether participants with different levels of diabetes-related DNA methylation at ABCG1 might respond differently to dietary weight-loss interventions with long-term changes in adiposity and body fat distribution. RESEARCH DESIGN AND METHODS The current study included overweight/obese participants from the POUNDS Lost trial. Blood levels of regional DNA methylation at ABCG1 were

OBJECTIVE We conducted a cluster-randomized, shared decision-making (SDM) trial offering lifestyle change, metformin, or both options, to adults at risk for diabetes in a primary care network (n = 20 practices). RESEARCH DESIGN AND METHODS We used propensity score matching to identify control patients and used electronic health record data to compare weight loss at 24 and 36 months of follow-up and

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OBJECTIVE Dietary glycemic index (GI) and glycemic load (GL) are associated with cardiometabolic health in children and adolescents, with potential distinct effects in people with increased BMI. DNA methylation (DNAm) may mediate these effects. Thus, we conducted meta-analyses of epigenome-wide association studies (EWAS) between dietary GI and GL and blood DNAm of children and adolescents. RESEARCH

OBJECTIVE To evaluate the relationship between social needs and metformin use among adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In a prospective cohort study of adults with T2D (n = 722), we linked electronic health record (EHR) and Surescripts (Surescripts, LLC) prescription network data to abstract data on patient-reported social needs and to calculate metformin adherence based

OBJECTIVE To determine the extent to which changes in plasma proteins, previously predictive of cardiometabolic outcomes, predict changes in two diabetes remission trials. RESEARCH DESIGN AND METHODS We applied SomaSignal predictive tests (each derived from ∼5,000 plasma protein measurements using aptamer-based proteomics assay) to baseline and 1-year samples of trial intervention (Diabetes Remission

Many people living with diabetes also have non-alcoholic fatty liver disease (NAFLD). Interleukin-6 (IL-6) is involved in both diseases, interacting with both membrane-bound (classical) and circulating soluble receptors (trans-signaling). We investigated whether secretion of IL-6 trans-signaling co-receptors are altered in NAFLD by diabetes, and whether this might associate with the severity of fatty

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Background Remission of type 2 diabetes can occur as a result of weight loss and is characterised by liver fat and pancreas fat reduction and recovered insulin secretion. In this analysis, we aimed to investigate the mechanisms of weight loss- induced remission in people with prediabetes. Methods In this prespecified post-hoc analysis, weight loss-induced resolution of prediabetes in the randomised

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, influencing numerous regulatory axes and extrahepatic vital organs. The molecular mechanisms that lead to the progression of NAFLD remain unclear and knowledge on the pathways causing hepatocellular damage followed by lipid accumulation is limited. Recently, a number of studies have shown that mRNA N6-methyladenosine

Fasting levels of glucose and susceptibility to type 2 diabetes mellitus (T2DM) are known to have a large genetic component. Genome-wide association studies (GWASs) have identified hundreds of loci associated with these traits. However, glucose homeostasis is highly complex, so there are likely to be many more loci that influence how blood levels of glucose are regulated. A study has now taken the

Women and men have different risk profiles for certain health conditions. For instance, differences in body composition between men and women are thought to partially underlie the different cardiometabolic risk profiles of men and women. Although men and women have similar levels of risk of obesity, their distribution of body adipose tissue differs. Men tend to carry excess weight as visceral adipose

OBJECTIVE Type 2 diabetes (T2D) is a major driver of chronic diseases around the globe. The aim was to assess the impact of T2D on the outcomes of solid organ transplantations. RESEARCH DESIGN AND METHODS We used the Scientific Registry of Transplant Recipients from 2006 to 2021 to collect data for all patients age ≥18 years who received a lung, heart, liver, or kidney transplant in the U.S. RESULTS

OBJECTIVE To investigate associations between age at natural menopause, particularly premature ovarian insufficiency (POI; natural menopause before age 40 years), and incident type 2 diabetes (T2D) and identify any variations by ethnicity. RESEARCH DESIGN AND METHODS We pooled individual-level data of 338,059 women from 13 cohort studies without T2D before menopause from six ethnic groups: White (n

Metabolic abnormalities are a hallmark of cancer cells and are essential to tumor progression. Oncometabolites have pleiotropic effects on cancer biology and affect a plethora of processes, from oncogenesis and metabolism to therapeutic resistance. Targeting oncometabolites, therefore, could offer promising therapeutic avenues against tumor growth and resistance to treatments. Recent advances in characterizing

OBJECTIVE To quantify the prevalence of diabetes and barriers to care among U.S. migrant farmworkers (i.e. those who travel from their permanent residence for seasonal farmwork). RESEARCH DESIGN AND METHODS Age-adjusted prevalence of self-reported diabetes and barriers to care were calculated among adult U.S. farmworkers from 2008 to 2017 National Agricultural Workers Surveys. RESULTS Among 16,913

OBJECTIVE The alignment between environmental stimuli (e.g., dark, light) and behavior cycles (e.g., rest, activity) is an essential feature of the circadian timing system, a key contributor to metabolic health. However, no previous studies have investigated light-activity alignment in relation to glycemic control in human populations. RESEARCH DESIGN AND METHODS The analysis included ∼7,000 adults

BACKGROUND Blood glucose regulation in women with diabetes may change during and after menopause, which could be attributed, in part, to decreased estrogen levels. PURPOSE To determine the effect of postmenopausal hormone therapy (HT) on HbA1c, fasting glucose, postprandial glucose, and use of glucose-lowering drugs in women with type 1 and women with type 2 diabetes. DATA SOURCES We conducted a systematic

Current guidelines recommend that individuals with diabetes receive yearly eye exams for detection of referable diabetic retinopathy (DR), one of the leading causes of new-onset blindness. For addressing the immense screening burden, artificial intelligence (AI) algorithms have been developed to autonomously screen for DR from fundus photography without human input. Over the last 10 years, many AI

Exercise has systemic health benefits through effects on multiple tissues, with intertissue communication. Recent studies indicate that exercise may improve breastmilk composition and thereby reduce the intergenerational transmission of obesity. Even if breastmilk is considered optimal infant nutrition, there is evidence for variations in its composition between mothers who are normal weight, those

OBJECTIVE To compare cardiac computed tomography (CT) with invasive coronary angiography (ICA) as the initial strategy in patients with diabetes and stable chest pain. RESEARCH DESIGN AND METHODS This prespecified analysis of the multicenter DISCHARGE trial in 16 European countries was performed in patients with stable chest pain and intermediate pretest probability of coronary artery disease. The

The importance of glucokinase (GK) in the regulation of insulin secretion has been highlighted by the phenotypes of individuals with activating and inactivating mutations in the glucokinase gene (GCK). Here we report 10 cases of congenital hyperinsulinism (HI) caused by eight unique activating mutations of GCK. Six are novel and near previously identified activating mutations sites. The first recognized

Maternal (m) consumption of a Western-style diet (WD) during pregnancy alters fatty-acid metabolism and reduces insulin sensitivity in fetal skeletal muscle. The long-term impact of these fetal adaptations and the pathways underlying disordered lipid metabolism are incompletely understood. Therefore, we tested whether a mWD chronically fed to lean, insulin sensitive adult Japanese macaques throughout

Insulin activates insulin receptor (IR) signaling and subsequently triggers IR endocytosis to attenuate signaling. Cell division regulators MAD2, BUBR1, and p31comet promote IR endocytosis upon insulin stimulation. Here, we show that genetic ablation of the IR–MAD2 interaction in mice delays IR endocytosis, increases IR levels, and prolongs insulin action at the cell surface. This in turn causes a

Type 2 diabetes is associated with cognitive impairment and a twofold increased risk of dementia compared to age-matched individuals without diabetes. Given that the eye and the brain share similar embryologic origin and anatomical features the retina offers a unique “window” to the brain. In this study we wanted to determine whether there was a difference in retinal imaging-based neuronal and vascular

Both long- and short-term glycemic variability have been associated with incident diabetes complications. We evaluated their relative and potential additive effects on incident renal complications in the Action to Control Cardiovascular Risk in Diabetes trial. A marker of shortterm glycemic variability 1,5-anhydroglucitol (1,5-AG) was measured in 4,000 random 12-months post-randomization plasma samples

The number of patients with type 2 diabetes mellitus (T2DM) is rising at an alarming rate. Regular physical activity and exercise are cornerstones in the therapy of T2DM. While a one-size-fits-all approach fails to account for many between-subject differences, the use of personalized exercise medicine has the potential of optimizing health outcomes. Here, a road map for personalized exercise therapy

Aggression is a well-studied social behavior that is universally exhibited by animals across a wide range of contexts. Prevailing knowledge suggests gonadal steroids primarily mediate aggression; however, this is based mainly on studies of male–male aggression in laboratory rodents. When males and females of other species, including humans, are examined, a positive relationship between gonadal steroids

Hemopexin (HPX) is overexpressed in the retina of diabetic patients, and induces the breakdown of the blood-retinal barrier (BRB) in vitro. The present study was aimed at evaluating whether HPX blockade by specific antibodies (aHPX) could avoid vascular leakage in vivo and microvascular angiogenesis in vitro and ex vivo. For this purpose, the effect of intravitreal injections (IVT) of aHPX on vascular

There is clinical evidence that increased urinary serine proteases are associated with the disease severity in the setting of diabetic nephropathy (DN). Elevation of serine proteases may mediate [Ca2+]i dynamics in podocytes through the protease-activated receptors (PARs) pathway, including associated activation of non-specific cation channels. Cultured human podocytes and freshly isolated glomeruli

OBJECTIVE Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. RESEARCH DESIGN AND METHODS ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was

OBJECTIVE Experimental evidence suggests that metabolic syndrome (MetS) is associated with changes in cardiac metabolism. Whether this association occurs in humans is unknown. RESEARCH DESIGN AND METHODS 821 asymptomatic individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study (50.6 [46.9–53.6] years, 83.7% male) underwent two whole-body 18F-fluorodeoxyglucose positron emission

A thorough understanding of the mechanisms controlling energy homeostasis is needed to prevent and treat metabolic morbidities. While the contribution of organs such as the liver, muscle, adipose tissue, and pancreas to the regulation of energy has received wide attention, less is known about the interplay with the nervous system. Here, we highlight the role of the nervous systems in regulating metabolism

Thyroid hormone replacement is paramount in overt hypothyroidism; recently, however, thyroid hormone substitution is increasingly prescribed to patients with normal thyroid hormone levels. This forum article discusses the complex causes and the possible negative effects of overusing thyroid hormone replacement drugs.

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Circadian rhythms, which are influenced by the light and dark that an organism is exposed to, have important effects on physiology. Traditionally, laboratory studies of circadian rhythms have used a 12-h light and 12-h dark experimental set up (photoperiod). However, apart from regions close to the Equator, the photoperiod varies throughout the year. A study in Cell Metabolism has now investigated

Deficiencies in leptin signalling cause severe early-onset obesity due to hyperphagia. A new study has investigated the long-term clinical outcomes for children with leptin signalling deficiency who do not receive treatment for the condition.

A new study in Nature has used a comprehensive multi-omics strategy in humans to uncover mechanisms by which carbohydrate metabolism by the gut microbiota contributes to insulin resistance.

Acute inflammation triggers activation of the hypothalamic–pituitary–adrenal axis, but whether it could also impede the adrenocortical response to adrenocorticotropic hormone remains controversial. A new study using preclinical models of acute inflammation demonstrates dysregulation of energy metabolism in adrenocortical cells, resulting in oxidative stress that induces disruption of steroidogenesis

In a new study, an ambulatory microdialysis system combined with ultrasensitive liquid chromatography-tandem mass spectrometry enabled the building of a 24-h high-resolution profile of adrenal steroids in the tissue by sampling interstitial fluid in 214 healthy volunteers. Daily and ultradian variations of eight free steroids, including cortisol and aldosterone, have been demonstrated, which opens

OBJECTIVE We validated longitudinally a typology of diabetes-specific family functioning (named Collaborative and Helpful, Satisfied with Low Involvement, Want More Involvement, and Critically Involved) in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted k-means cluster analyses with nine dimensions to determine if the typology replicated in a diverse sample and if type assignment