Robert V Considine

• Indiana University – Purdue University Indianapolis

Background Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk. Methods Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and ele...

Objective Bariatric surgery reduces sweet‐liking, but mechanisms remain unclear. We examined related brain responses. Methods A total of 24 nondiabetic bariatric surgery and 21 control participants with normal weight to overweight were recruited for an observational controlled cohort study. They underwent sucrose taste testing outside the scanner...

Background and Aims: Identifying simple markers of risk for worsening glucose can allow care providers to target therapeutic interventions according to risk of worsening glycemic control. We aimed to determine which routine clinical measures herald near-term glycemic worsening in early type 2 diabetes(T2D). Methods: The Early Diabetes Intervention...

Background: Treatments that delay progression of cognitive impairment in older adults are of great public health significance. This manuscript outlines the protocol, recruitment, baseline characteristics, and retention for a randomized controlled trial of cognitive and aerobic physical training to improve cognition in individuals with subjective c...

Although depression is a risk and prognostic factor for cardiovascular disease (CVD), clinical trials treating depression in patients with CVD have not demonstrated cardiovascular benefits. We proposed a novel explanation for the null results for CVD-related outcomes: the late timing of depression treatment in the natural history of CVD. Our object...

The somatic depressive symptom cluster (including appetite and sleep disturbances) is more strongly associated with insulin resistance (a diabetes risk marker) than other depressive symptom clusters. Utilizing baseline data from 129 primary care patients with depression but no diabetes in the eIMPACT trial (Mage = 59 years, 78% female, 50% Black),...

Bariatric surgery causes marked changes in eating behavior, including reduced preference for highly sweet foods. No studies have addressed the brain response to receipt of this primary taste modality following weight loss surgery. Eighteen women (BMI 47.5±7.6 kg/m2, age 43.1±10.2 y) rated perceived intensity and liking of sucrose solutions (0, 0.1,...

Short sleep is associated with obesity risk. Experimental studies with adults and observational studies with children demonstrate that changes in eating, including increased caloric intake from energy-dense foods and sugar-sweetened beverages as well as increased caloric intake in the evening, may partially account for this increased risk. We there...

Inflammation and dyslipidemia are often present in Polycystic Ovary Syndrome (PCOS). We determined the effect of saturated fat ingestion on circulating heat shock protein-70 (HSP-70) and mononuclear cell (MNC) toll-like receptor-2 (TLR2) gene expression, activator protein-1 (AP-1) activation and matrix matalloproteinase-2 (MMP-2) protein in women w...

Objectives The purpose of this study was to determine if the mixed evidence of almond consumption on HbA1c stems from testing people with different body fat distributions (BFD) associated with different risks of glucose intolerance. Methods A 6-month RCT in 134 adults was conducted. Participants were randomly assigned to the almond or control trea...

The purpose of this study was to determine if the mixed evidence of almond consumption on HbA1c stems from testing people with different body fat distributions (BFD) associated with different risks of glucose intolerance. A 6-month RCT in 134 adults was conducted. Participants were randomly assigned to the almond (A) or control (C) group based on t...

The Disposition Index, calculated by multiplying measures of insulin secretion and insulin sensitivity, is widely applied as a sensitivity-adjusted measure of insulin secretion. We have recently shown that linearizing the underlying relationship uniquely permits identification of terms relating to maximal insulin secretion capacity and the secretio...

Oxidative stress (OS) and Inflammation are often present in polycystic ovary syndrome (PCOS). We examined the effects of salsalate treatment on nutrient-induced OS and inflammation, ovarian androgen secretion, ovulation and insulin sensitivity. Eight lean insulin-sensitive women with PCOS and 8 age- and body composition-matched ovulatory controls f...

Replacement of islets/β cells that provide long-lasting glucose-sensing and insulin-releasing functions has the potential to restore extended glycemic control in individuals with type 1 diabetes. Unfortunately, persistent challenges preclude such therapies from widespread clinical use including cumbersome administration via portal vein infusion, si...

Objectives The purpose of this study was to determine if the mixed evidence of almond consumption on long term glycemic control stems from testing people with different body fat distributions. Methods A 6-month randomized controlled trial in 118 adults was conducted. Participants were randomly assigned to the almond or control group based on their...

Study question: What is the effect of saturated fat ingestion on mononuclear cell (MNC) TNFα, IL-6 and IL-1β secretion and circulating IL-6 levels in women with polycystic ovary syndrome (PCOS)? Summary answer: Women with PCOS exhibit increases in MNC-derived TNFα, IL-6 and IL-1β secretion and circulating IL-6 following saturated fat ingestion e...

Objective Pulmonary hypertension (PH) due to left heart disease (group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide; however, at present, there is no proven effective therapy available for its treatment. PH-HFpEF is associated with insulin resistance and features o...

Context Inflammation and insulin resistance are often present in Polycystic Ovary Syndrome (PCOS). Objective We determined the effect of saturated fat ingestion on mononuclear cell (MNC) nuclear factor-κB (NFκB) activation, NFκB, inhibitory-κBα (IκBα) and TNFα gene expression, and circulating C-reactive protein (CRP) in women with PCOS. Design Cr...

Bariatric surgery is known to attenuate glomerular hyperfiltration over the long term and thereby protect the kidney from mechanical damage. Whether this effect is directly related to weight loss or is independent of weight as are some of its other beneficial metabolic effects is not known. We explored this question in a preliminary study that dire...

Background and Hypothesis: In pathologic states such as obesity and insulin resistance, there is a progressive decline in insulin sensitivity requiring greater insulin secretion to maintain normoglycemia. The inverse relationship between insulin sensitivity and secretion is mathematically defined by the Disposition Index (DI), a measure of βcell fu...

Context Oxidative stress and insulin resistance are often present in Polycystic Ovary Syndrome (PCOS). Objective We determined the effect of saturated fat ingestion on leukocytic reactive oxygen species (ROS) generation and p47phox expression, and circulating thiobarituric substances (TBARS) in women with PCOS. Design Cross-sectional study. Sett...

Background: Multiple national organizations and leaders have called for increased attention to dementia prevention in those most vulnerable, for example persons with limited formal education. Prevention recommendations have included calls for multicomponent interventions that have the potential to improve both underlying neurobiological health and...

Reliable clinical indicators of near-term risk of worsening glycemia in type 2 diabetes (T2D) could help guide individual-level interventions. Here we analyzed data from the Early Diabetes Intervention Program (EDIP) to identify predictors of near-term glycemic progression. EDIP evaluated progression of fasting blood glucose (FBG) above 140 mg/dl o...

How sweet taste perception promotes excess caloric intake, obesity and diabetes is debated. There is little evidence for altered sweet taste in obesity, and adiposity does not predict sweet liking. However, overweight and obese subjects generally prefer high fat, sweet stimuli. The effect of adiposity on brain responses to sweet taste has not been...

Context Inflammation and insulin resistance are often present in Polycystic Ovary Syndrome (PCOS). Objective We determined the effect of saturated fat ingestion on circulating lipopolysaccharide (LPS) and mononuclear cell (MNC) toll-like receptor-4 (TLR-4) and suppressor of cytokine signaling-3 (SOCS-3) in women with PCOS. Design Cross-sectional...

Objective: Abnormally elevated proinsulin secretion has been reported in type 2 and early type 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing type 1 diabetes and low or absent C-peptide secretory capacity retained the ability to make proinsulin. Research design and methods: C-peptide and pr...

Context Glucagon-like peptide-1 (GLP-1) and the clinically available GLP-1 agonists have been shown to exert effects on the heart. It is unclear whether these effects occur at clinically used doses in vivo in humans, possibly contributing to CVD risk reduction. Objective To determine whether liraglutide at clinical dosing augments myocardial gluco...

Widespread use of pancreatic islet transplantation for treatment of type 1 diabetes (T1D) is currently limited by requirements for long-term immunosuppression, limited donor supply, and poor long-term engraftment and function. Upon isolation from their native microenvironment, islets undergo rapid apoptosis, which is further exacerbated by poor oxy...

The low digestibility and high satiety effects of nuts have been partly attributed to mastication. This work examines chewing forces and the bolus particle size of nuts (walnuts, almonds, pistachios) varying in physical properties under different conditions (with and without water, juice, sweetened yogurt and plain yogurt) along with satiety sensat...

Background Low-calorie sweeteners are often used to moderate energy intake and postprandial glycemia, but some evidence indicates that they may exacerbate these aims. Objective The trial's primary aim was to assess the effect of daily aspartame ingestion for 12 wk on glycemia. Effects on appetite and body weight were secondary aims. Methods One h...

A heightened hedonic response to sweet tastes has been associated with increased alcohol preference and alcohol consumption in both humans and animals. The principal goal of this study was to examine blood oxygenation level dependent (BOLD) activation to high- and low-concentration sweet solutions in subjects who are either positive (FHP) or negati...

Objective: Type 2 diabetes is a growing health problem among both adults and adolescents. To better understand the differences in the pathogenesis of diabetes between these groups, we examined differences in β-cell function along the spectrum of glucose tolerance. Research design and methods: We evaluated 89 adults and 50 adolescents with normal...

Background Glucose homeostasis improves within days following Roux-en-Y gastric bypass (RYGB) surgery. The dynamic metabolic response to caloric intake following RYGB has been assessed using liquid mixed meal tolerance tests (MMTT). Few studies have evaluated the glycemic and hormonal response to a solid mixed meal in subjects with diabetes prior t...

Background: Retinopathy is increasingly recognized in prediabetic populations, and may herald increased risk of metabolic worsening. The Early Diabetes Intervention Program (EDIP) evaluated worsening of glycemia in screen-detected Type 2 diabetes, following participants for up to 5years. Here we have evaluated whether the presence of retinopathy a...

Context: Evidence-based strategies to prevent progression of dysglycemia in newly diagnosed type 2 diabetes are needed. Objective: To undertake a secondary analysis of the Early Diabetes Intervention Program (EDIP) to understanding the features that were protective against worsening glycemia. Design: EDIP was a randomized, placebo controlled t...

Background: Paediatric observational studies demonstrate associations between sleep, television viewing and potential changes in daytime activity levels. Objective(s): To determine whether experimental changes in sleep lead to changes in children's sedentary and physical activities. Methods: Using a within-subject counterbalanced design, 37 ch...

Introduction: Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted...

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human Type 2 Diabetes (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation (16-(18)F-fluor...

Consuming alcohol prior to a meal (an apéritif) increases food consumption. This greater food consumption may result from increased activity in brain regions that mediate reward and regulate feeding behavior. Using functional magnetic resonance imaging, we evaluated the blood oxygenation level dependent (BOLD) response to the food aromas of either...

In the first studies of leptin administration to obese mice it was noted that low dose leptin, which did not alter food intake or body weight, decreased blood glucose. This observation initiated investigation into the mechanisms through which leptin regulated intermediary metabolism independent of effects on caloric intake and body weight. With lep...

Shortly following the discovery of leptin methods were developed to measure this novel adipokine in the circulation. The finding of multiple splice variants of the leptin receptor gene, including an mRNA for a soluble leptin receptor, suggested the presence of a circulating leptin binding protein. It was subsequently demonstrated that leptin associ...

Leptin is a 16 kDa hormone synthesized and released by adipose tissue. The primary receptor for leptin is located in the central nervous system. Circulating leptin levels increase in proportion to the amount of body fat, and are greater in women than men. Leptin inhibits food intake and reduces body fat in animal models, but is not an effective wei...

Significance Chronic low-grade inflammation plays a causative role in obesity-associated metabolic diseases. However, the mechanisms underlying chronicity of low-grade inflammation remain elusive. Herein, we identify inhibitor of κB kinase epsilon (IKBKE) as a new modulator of chronic inflammation in macrophages. We first show that IKBKE is clinica...

To evaluate whether the augmented insulin and glucose response to a glucose challenge is sufficient to compensate for defects in glucose utilization in obesity and type 2 diabetes, using a breath test measurement of integrated glucose metabolism. Non-obese, obese normoglycemic and obese type 2 diabetic subjects were studied on 2 consecutive days. A...

Background The ability of interventions to affect declining β-cell function in screen-detected type 2 diabetes are poorly described. The Early Diabetes Intervention Program (EDIP; ClinicalTrials.gov NCT01470937) was a randomized study based on the hypothesis that improving postprandial glucose excursions with acarbose would slow the progression of...

There is considerable interest in the role of sleep in weight regulation, yet few studies have examined this relationship in overweight/obese (OW/OB) adults. Using a within-subject, counterbalanced design, 12 OW/OB women were studied in lab with two nights of short (5 hr time in bed [TIB]) and two nights of long (9 hr TIB) sleep. Hunger, consumptio...

Objective: Because of lack of evidence, we aimed to examine to what degree low-grade systemic inflammation and coronary heart disease (CHD) death shared common genetic and environmental substrates. Approach and results: From the 41-year prospective National Heart, Lung, and Blood Institute Twin Study, we included 950 middle-aged male twins at ba...

Sensory properties of foods promote and guide consumption in hunger states, whereas satiation should dampen the sensory activation of ingestive behaviors. Such activation may be disordered in obese individuals. Using functional magnetic resonance imaging (fMRI), we studied regional brain responses to food odor stimulation in the sated state in obes...

Introduction: Whole diet evaluated using dietary pattern is associated with systemic inflammation and coronary heart disease (CHD). Systemic inflammation also contributes to CHD risk. Genetic factors explain variations in whole diet, systemic inflammation, and CHD. However, it is unknown whether systemic inflammation is a mechanism linking whole di...

In this study, we used lentiviral-delivered shRNA to generate a clonal line of 3T3-F442A preadipocytes with stable silencing of Hepatocyte Growth Factor (HGF) expression, and examined the long-term consequence of this modification on fat pad development. HGF mRNA expression was reduced 94%, and HGF secretion 79% (P<0.01), compared to preadipocytes...

Context:Adipose tissue is a highly active endocrine organ that secretes many factors that affect other tissues and whole-body metabolism. Adipocytes are responsive to several glycoprotein 130 (gp130) cytokines, some of which have been targeted as potential antiobesity therapeutics.Objective:Oncostatin M (OSM) is a gp130 family member known to inhib...

Objective: To examine the effect of experimental changes in children's sleep duration on self-reported food intake, food reinforcement, appetite-regulating hormones, and measured weight. Methods: Using a within-subjects, counterbalanced, crossover design, 37 children, 8 to 11 years of age (27% overweight/obese) completed a 3-week study. Children...

The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represents an adaptive response that preserves WAT lipid homeostasis in...

Background: Exhaled (13)CO2 following ingestion of [(13)C]glucose with a standard oral glucose tolerance load correlates with blood glucose values but is determined by tissue glucose uptake. Therefore exhaled (13)CO2 may also be a surrogate measure of the whole-body glucose disposal rate (GDR) measured by the gold standard hyperinsulinemic euglyce...

Chewing reportedly contributes to satiation and satiety signals. Attempts to document and quantify this have led to small and inconsistent effects. The present trial manipulated oral processing effort though required chewing of gums of different hardness and measured appetitive sensations, energy intake, gastric emptying, GI transit time, and conce...

Glucagon-like peptide 1 (GLP-1) has insulin-like effects on myocardial glucose uptake which may contribute to its beneficial effects in the setting of myocardial ischemia. Whether these effects are different in the setting of obesity or type 2 diabetes (T2DM) requires investigation. We examined the cardiometabolic actions of GLP-1 (7-36) in lean an...

The antidiabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. The Early Diabetes Intervention Program (EDIP) was a randomized trial of acarbose versus placebo, in 219 participants with early dia...

Objective: Plasma Hepatocyte Growth Factor (HGF) is significantly elevated in obesity and may contribute to vascular disease, metabolic syndrome or cancer in obese individuals. The current studies were done to determine if hyperinsulinemia increases plasma HGF. Materials/methods: Twenty-two participants (10 women/12 men, BMI 20.6-34.5 kg/m(2), a...

The angiogenic inhibitor TNP-470 attenuates high-fat diet-induced obesity; however, it is not clear how the compound alters energy balance to prevent weight gain. Five-week-old C57BL/6J mice were fed high-fat diet (45% energy from fat) for 6.5 weeks and treated with TNP-470 (20 mg/kg body weight; n = 7) or vehicle (saline; n = 7). Control mice (n =...

INTRODUCTION: Alcohol consumption is associated with coronary heart disease (CHD), and systemic inflammation also contributes to CHD risk. It is unknown to what extent systemic inflammation plays a role in the association between alcohol consumption and CHD. We examined the hypothesis that systemic inflammation mediated the relationship between usu...

Beverage consumption is implicated in the overweight/obesity epidemic through the weaker energy compensation response it elicits compared with solid food forms. However, plausible mechanisms are not documented. This study assessed the cognitive and sensory contributions of differential postingestive responses to energy- and macronutrient-matched li...

HDL is a heterogeneous mixture of lipoprotein particles varying in composition, size, and function. We and others have described a small (7.0nm), minor (0.1% of total apolipoprotein AI) particle containing apolipoprotein AI, AIV and glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) in humans the function of which is not entirely known...

Food aromas are signals associated with both food's availability and pleasure. Previous research from this laboratory has shown that food aromas under fasting conditions evoke robust activation of medial prefrontal brain regions thought to reflect reward value (Bragulat et al., Obesity (Silver Spring), 18(8): 1566–1571, 2010). In the current study,...

Obesity is associated with hyperparathyroidism and increased bone mass and turnover, but their pathogeneses are unclear. Our aim was to determine in obesity interrelationships among serum levels of leptin, the mineral-regulating hormones, bone turnover markers, and sclerostin. This case-control study was performed in 20 women having bariatric surge...

Diminished cortical filamentous actin (F-actin) has been implicated in skeletal muscle insulin resistance, yet the mechanism(s) is unknown. Here we tested the hypothesis that changes in membrane cholesterol could be a causative factor, as organised F-actin structure emanates from cholesterol-enriched raft microdomains at the plasma membrane. Skelet...