Michelle Van Name

Leptin Is Associated With Exaggerated Brain Reward and Emotion Responses to Food Images in Adolescent Obesity

OBJECTIVE In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation’s youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors. RESEARCH DESIGN AND METHODS Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. RESULTS Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE). CONCLUSIONS This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D.

Mitigating Meal-Related Glycemic Excursions in an Insulin-Sparing Manner During Closed-Loop Insulin Delivery: The Beneficial Effects of Adjunctive Pramlintide and Liraglutide.

OBJECTIVE Closed-loop (CL) insulin delivery effectively maintains glucose overnight but struggles when challenged with meals. Use of single-day, 30-μg/meal pramlintide lowers meal excursions during CL. We sought to further elucidate the potential benefits of adjunctive agents after 3–4 weeks of outpatient dose titration. RESEARCH DESIGN AND METHODS Two CL studies were conducted: one evaluating adjunctive pramlintide and the other liraglutide. Ten subjects (age 16–23 years; A1C 7.2 ± 0.6% [55 ± 6.6 mmol/mol]) completed two 24-h sessions: one on CL alone and one on CL plus 60-μg pramlintide (CL + P), after a 3–4-week outpatient dose escalation. Eleven subjects (age 18–27 years; A1C 7.5 ± 0.9% [58 ± 9.8 mmol/mol]) were studied before and after treatment with 1.8 mg liraglutide (CL + L) after a similar 3–4-week dose escalation period. Timing and content of meals during CL were identical within experiments; meals were not announced. RESULTS Pramlintide delayed the time to peak plasma glucose (PG) excursion (CL 1.6 ± 0.5 h vs. CL + P 2.6 ± 0.9 h, P < 0.001) with concomitant blunting of peak postprandial increments in PG (P < 0.0001) and reductions in postmeal incremental PG area under the curve (AUC) (P = 0.0002). CL + L also led to reductions in PG excursions (P = 0.05) and incremental PG AUC (P = 0.004), with a 28% reduction in prandial insulin delivery. Outpatient liraglutide therapy led to a weight loss of 3.2 ± 1.8 kg, with a 26% reduction in total daily insulin dose. CONCLUSIONS Adjunctive pramlintide and liraglutide treatment mitigated postprandial hyperglycemia during CL control; liraglutide demonstrated the additional benefit of weight loss in an insulin-sparing manner. Further investigations of these and other adjunctive agents in long-term outpatient CL studies are needed.

Hepatic De Novo Lipogenesis in Obese Youth Is Modulated by a Common Variant in the GCKR Gene

OBJECTIVE This studys aim was to evaluate whether the GCKR rs1260326 variant increases hepatic de novo lipogenesis (DNL). SETTING AND DESIGN To test this hypothesis, 14 adolescents, seven homozygous for the common allele (CC) and seven homozygous for the risk allele (TT), underwent measurement of hepatic DNL during the fasting state and after consumption of a carbohydrate (CHO) drink (75 g glucose and 25 g fructose). DNL was assessed through incorporation of deuterium in the palmitate contained in the very low-density lipoprotein. RESULTS Subjects with TT demonstrated higher fasting fractional DNL (P = .036) and a lower increase in fractional DNL after the CHO challenge (P = .016). With regard to absolute lipogenesis, TT subjects had both higher fasting rates (P = .015) and 44% greater area under the curve of absolute lipogenesis during the study (P = .016), compared to CC subjects. Furthermore, subjects carrying the TT genotype showed higher basal rates of glucose oxidation (P = .0028) and a lower ability than CC subjects to increase the rates of glucose oxidation after the CHO load (P = .054). CONCLUSIONS This study reports for the first time rates of DNL in obese adolescents and suggests that the GCKR rs1260326 gene variant, which is associated with greater glycolysis, increases hepatic DNL. These data highlight the role of glycolytic carbon flux in liver lipid synthesis and hypertriglyceridemia in these youngsters.

Blunted Suppression of Acyl-Ghrelin in Response to Fructose Ingestion in Obese Adolescents: the Role of Insulin Resistance

Fructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared with glucose ingestion. This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity.

Moving toward the ideal insulin for insulin pumps.

Advances in insulin formulations have been important for diabetes management and achieving optimal glycemic control. Rapid-acting insulin analogs provide a faster time−action profile than regular insulin and are approved for use in pumps. However, the need remains for therapy to deliver a more physiologic insulin profile. New insulin formulations and delivery methods are in development, with the aim of accelerating insulin absorption to accomplish ultra-fast-acting insulin time−action profiles. Furthermore, the integration of continuous glucose monitoring with insulin pump therapy enables on-going adjustment of insulin delivery to optimize glycemic control throughout the day and night. These technological and pharmacological advances are likely to facilitate the development of closed-loop pump systems (i.e., artificial pancreas), and improve glycemic control and quality of life for patients with diabetes.

Nighttime is the worst time: Parental fear of hypoglycemia in young children with type 1 diabetes

Fear of hypoglycemia is common in parents of young children with type 1 diabetes (T1D), but little is known about the specific fears that parents most often experience. Hypoglycemia fear has been associated with poorer glycemic control in older children, though not yet studied in a large cohort of very young children.

Type 2 diabetes mellitus in pediatrics: a new challenge.

BackgroundThe increased prevalence of childhood obesity in the last few years has been accompanied by the increase in prevalence of type 2 diabetes in pediatrics. In this paper, we will review the risk factors and the pathogenic determinants leading to type 2 diabetes in youth.Data sourcesWe searched on PubMed with the key words: obesity, type 2 diabetes, children, adolescents, youth, non-alcoholic fatty liver disease, genes and selected those publications written in English that we judged to be relevant to the topic of the review.ResultsBased on the data present in the literature, we reviewed the following three topics: 1) the role of ectopic fat deposition, in particular of fatty liver, in the pathogenesis of pediatric type 2 diabetes; 2) the progression to type 2 diabetes in pediatrics and how it differs from adults, and 3) current theraputic options.ConclusionType 2 diabetes in youth is a complex disease, creating new challenges in treatment and prevention.

Schooling diabetes: Use of continuous glucose monitoring and remote monitors in the home and school settings

Despite significant advances in type 1 diabetes (T1D) management, achieving targeted glycemic control in pediatric patients remains a struggle. Continuous glucose monitoring (CGM) with remote access holds the promise to address this challenge by allowing caregivers to monitor glucose, even when the child is not directly under their supervision.

Understanding bolus insulin dose timing: the characteristics and experiences of people with diabetes who take bolus insulin

Abstract Objective: Despite the increased popularity of newer, fast-acting bolus insulin treatment options that allow for more flexibility in the timing of bolus insulin dosing in recent years, relatively little is known about people with diabetes who administer bolus insulin at differing times in relation to their meals. The purpose of this study was to investigate bolus insulin dose timing in relation to meals among people with type 1 (T1D) and type 2 (T2D) diabetes, as well as to better understand the characteristics and experiences of people who bolus dose at differing times. Methods: A web-based survey of adults with T1D and T2D treated with bolus insulin therapy in Germany, the UK, and USA was conducted. Results: A total of 906 respondents completed the survey (39% T1D; 61% T2D). A majority of respondents reported bolus dosing before meals in the previous week (57.0%), followed by after meals (18.9%), with meals (12.7%), and at varying times (11.5%). Compared to respondents who dosed with or after meals, those who dosed before meals were significantly less likely to experience hypoglycemia (before, 55.7%; with, 72.8%; after, 68.7%; p < .001) in the previous week. Respondents who bolus dosed before meals were significantly more likely to perceive bolus dose timing as flexible (45.5%) compared to those who dosed with (27.8%) or after (35.7%) meals (p < .001). Conclusion: Results show that many people with T1D and T2D dose their bolus insulin with or after meals. Key limitations of all self-report surveys include potential bias in responses and generalizability of findings. However, the study was designed to help mitigate these limitations. The findings have implications for clinicians and suggest opportunities for improving diabetes education and care.

Eligibility for clinical trials is limited for youth with type 2 diabetes: Insights from the Pediatric Diabetes Consortium T2D Clinic Registry

Restrictive eligibility criteria have hampered enrollment into trials for new drugs for youth with type 2 diabetes (T2D). We utilized Pediatric Diabetes Consortium (PDC) T2D Registry enrollment data to estimate the percentage of patients who would be excluded from current T2D trials based on out‐of‐range HbA1c levels. We also examined whether well‐controlled patients could be included because baseline HbA1c would rise during a 6 to 12‐month study if assigned to control group.