Session Details Interrelations of Youth Obesity, Type 2 Diabetes

Obesity contributes to development of youth-onset type 2 diabetes (T2D) and can lead to detrimental health outcomes in adulthood. Researchers explored this relationship and offered insights on addressing the problem during a session at the American Diabetes Association’s (ADA) 80th Scientific sessions, held virtually due to coronavirus disease 2019 (COVID-19).

In the United States, obesity affects 1 in 5 children and adolescents, according to the CDC, while the risk of developing T2D is 4 times greater for obese children compared with those at normal weight.

The session began with a study comparing cerebral blood flow in obese youth with T2D and obese controls without T2D. Youth with T2D tend to have higher rates of vascular thickness and stiffness compared with peers with T1D, while youth onset T2D is associated with an increased risk of cardiovascular disease.

Using magnetic resonance imaging (MRIs), researchers found global cerebral blood flow was significantly lower in those with T2D compared with their obese euglycemic counterparts.¹ Blood flow was lower in 7 regions in the brain throughout the parietal, frontal, and temporal lobes (P < .01), while there were no brain regions in which blood flow was greater in youth with T2D. Imaging also revealed carotid intima medial thickness (IMT) was inversely correlated with cerebral blood flow in the T2D cohort. Researchers suggest longitudinal studies take place using larger cohorts to investigate the association between cerebral blood flow, cognitive function, and brain structure.

In a study of 35 obese youth with a Body Mass Index (BMI) above the 85th percentile (age 15.8 [SD 2.4]) researchers investigated the metabolic and genetic determinants of incretin effects in those with normal (n=18) and impaired (n=17) glucose intolerance.²

Prediabetes and T2D in obese youth are associated with a reduced incretin effect, defined as a greater insulin response to an oral vs. intravenous glucose load.

Investigators found “insulin clearance (P = .004), T allele for TCF7L2 (P = .018) and 2-h glucose (P = .035) were independent determinants of the incretin effect, with an increase in insulin clearance associated with greater incretin effect.” The low-incretin phenotype in obese youths is characterized by reduced beta cell function after the oral glucose load, low insulin sensitivity and clearance, and a higher 1-hour (1-h) glucose.

By identifying the low-incretin effect phenotype, providers may be able to target therapeutic interventions based on glucagon-like peptin-1 (GLP-1) analogues. “The use of 1-h glucose might provide a convenient cost-effective surrogate measure to identify this group and to define its longitudinal progression,” researchers concluded.

A separate³ randomized treatment trial of T2D in youth evaluated lipoprotein particle distribution, as T2D in adolescents is associated with an unfavorable lipid profile. The lipoprotein particle number and size were then related to glycated hemoglobin (A1C), need for insulin treatment, gender, race/ethnicity, BMI, and blood pressure.

Over 3 years, study participants (n=348) demonstrated increasing numbers of low-density lipoprotein (LDL), high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) particles (all P < .001).

In addition, A1C was strongly correlated with LDL, VLDL, and HDL particle number (all P < .005), while BMI and blood pressure exhibited a positive association with LDL, HDL, and VLDL particle numbers. According to researchers, the “data demonstrate an atherogenic lipoprotein phenotype in youth with T2D and strong relationships with glycemic control and other cardiac risk factors,” prompting concern of premature development of atherosclerosis in youth with T2D.

Future health complications resulting from T2D or obesity in youth can be severe.

In a 10-year study following 989 individuals, researchers discovered over 65% of children with initial obesity remained obese at follow-up while only 10.4% of non-obese children at baseline became obese.⁴

According to investigators, “adipokine dysregulation is an early biomarker of adipose tissue dysfunction, which has been shown to relate to metabolic health.”

Data showed decreased adiponectin and fibroblast growth factor 21 (FGF-21) levels and increased leptin were associated with obesity risk at baseline and 10-year follow-up (all P < .05), suggesting “certain aberrant patterns of adipokine regulation during childhood may serve as biomarkers for the subsequent development of obesity.”

Individuals with diabetes are also at high risk for heart failure with preserved ejection fraction (HFpEF) due to diabetic cardiomyopathy (DCM). DCM is defined as abnormal myocardial structure and function without the presence of overt coronary artery disease, and the condition can lead to diastolic dysfunction.

Researchers compared the potential for long-term health complications in young adults with T2D and type 1 diabetes (T1D)⁵.

Of 255 study participants with T1D (mean age 21.2 [5.2]) and 203 with T2D (mean age 24.3[4.3]), all were diagnosed with diabetes in childhood and had an average disease duration of 11 years. Data showed individuals with T2D exhibited:

• a worse cardiovascular risk profile (higher BMI, systolic and diastolic blood pressure, triglycerides, LDL-C, A1c and lower HDL-C) than those with T1D (all P < .05)
• lower left ventricular (LV) filling volume, transmitral velocity, and higher LV pressure (all P < .05), than those with T1D, suggesting worse diastolic function

“Given there are no effective treatments for HFpEF, our data suggest targeting modifiable risk factors may be useful to prevent further diastolic dysfunction,” they concluded.

One potential solution to the myriad of health complications resulting from youth obesity and T2D is a school-based program that promotes healthy eating and improves lifestyles⁶. Using a sticker-based food diary and colorful 12-page story book to motivate young children to adopt a healthier diet, researchers in Sri Lanka devised a novel school-based program for children ages 5 to 7.

The program was broken down by week. In the first week, children self-monitored their daily food intake at home via the food diary and received a Smiley Face Score (SFS) based on how healthy each meal was. Throughout the second week, teachers read the children’s books “illustrating the physical and psychosocial effects of obesity and benefits of healthy lifestyle in a child friendly manner.” Children completed the food diary again in the third week. To measure the program’s efficacy in improving healthy eating and lifestyle, researchers compared SFS of weeks 1 and 3. Class teachers and parents also completed anonymous grade-response and open response questionnaires.

In total, 1029 students completed food diaries and improvement in healthy eating was demonstrated by a mean SFS increase of 11.7% from week 1 to week 3. The study yielded the additional following results:

• SFS improved >10% in all BMI categories
• SFS improvement was greater in boys (13.0 vs 9.7, P = .02), and in second-graders compared with first-graders (13.1 vs 10.3, P = .045)
• The majority of responding parents (> 90%) and teachers (95%) strongly agreed/agreed that this program motivated children towards a healthier lifestyle and led to an observable improvement in food habits

“This novel program led to a demonstrable improvement in healthy lifestyle among 5 to 7-yearolds and was received favorably by parents and teachers,” researchers concluded. Encouraged by the favorable results, the Ministry of Education in Sri Lanka plans to implement the program nationwide throughout 2020-2021 school year, with an enrollment total of around 830,000 students.

References:

1. Redel JM, Difrancesco MW, Lee GR, et al. Cerebral blood flow is lower in youth with type 2 diabetes compared with obese controls. Presented at: American Diabetes Association 80^th Scientific Sessions; June 12-16, 2020; Abstract 55-OR. https://bit.ly/2UHV8ml
2. Galderisi A, Samuels S, Pierpont B, et al. Genetic and metabolic determinants of the incretin effect in obese adolescent with prediabetes. Presented at: American Diabetes Association 80th Scientific Sessions; June 12-16, 2020; Abstract 61-OR. https://bit.ly/2UFQUf0
3. Otvos JD, Drews K, Tesfaldet B, et al. Liproprotein particle distribution by NMR in youth with type 2 diabetes (T2D) in the TODAY study. Presented at American Diabetes Association 80th Scientific Sessions; June 12-16, 2020; Abstract 59-OR. https://bit.ly/2UGdNPu
4. Li M amd Willi SM. Childhood adipokine profiles predict the incidence and trajectory of obesity in young adults: the BCAMS study. Presented at American Diabetes Association 80^th Scientific Sessions; June 12-16, 2020; Abstract 62-OR. https://bit.ly/2XVIUbI
5. Dabela D, Dolan LM, Isom S, et al. Diastolic dysfunction, a precursor for heart failure in young adults with youth-onset type 1 and type 2 diabetes: the SEARCH for diabetes in youth study. Presented at American Diabetes Association 80^th Scientific Sessions; June 12-16, 2020; Abstract 58-OR. https://bit.ly/2UFPH7j
6. Sachchithananthan S, Angulugaha Gamage PS, Ramamoorthy S, et al. A novel school-based obsesity prevention program improves healthy eating/lifestyle among 5- to 7-year-olds. Presented at American Diabetes Association 80^th Scientific Sessions; June 12-16, 2020; Abstract 57-OR. https://bit.ly/37tGAvD