Obese Adolescents with Type 2 Diabetes Mellitus Have Hippocampal and Frontal Lobe Volume Reductions

Bruehl, Hannah; Sweat, Victoria; Tirsi, Aziz; Shah, Bina; Convit, Antonio

doi:10.4236/nm.2011.21005

Cited by 73 publications

(60 citation statements)

References 50 publications

(59 reference statements)

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“…7 The current finding of smaller hippocampal volumes among nondiabetic adolescents with MetS was unexpected. These data suggest that among obese adolescents the hippocampus may already be affected in the prediabetic stages of metabolic disease.…”

Section: Discussionmentioning

confidence: 60%

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Obesity and Metabolic Syndrome and Functional and Structural Brain Impairments in Adolescence

Yau¹,

Castro²,

Tagani³

et al. 2012

Pediatrics

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228

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WHAT'S KNOWN ON THIS SUBJECT: Despite the dramatic rise in prevalence of metabolic syndrome (MetS) among children and adolescents, and that MetS is associated with cognitive and brain impairments among adults, no data on the impact of MetS on the brain exist in children. WHAT THIS STUDY ADDS:It provides the first data on the impact of MetS on brain in adolescence. We show reductions in cognitive function and brain structural integrity in nondiabetic adolescents with MetS, thus suggesting that even pre-clinical metabolic illness may give rise to brain complications.abstract BACKGROUND: The prevalence of metabolic syndrome (MetS) parallels the rise in childhood obesity. MetS is associated with neurocognitive impairments in adults, but this is thought to be a long-term effect of poor metabolism. It would be important to ascertain whether these brain complications are also present among adolescents with MetS, a group without clinically manifest vascular disease and relatively short duration of poor metabolism. METHODS:Forty-nine adolescents with and 62 without MetS, matched on age, socioeconomic status, school grade, gender, and ethnicity, received endocrine, MRI, and neuropsychological evaluations. RESULTS:Adolescents with MetS showed significantly lower arithmetic, spelling, attention, and mental flexibility and a trend for lower overall intelligence. They also had, in a MetS-dose-related fashion, smaller hippocampal volumes, increased brain cerebrospinal fluid, and reductions of microstructural integrity in major white matter tracts. CONCLUSIONS:We document lower cognitive performance and reductions in brain structural integrity among adolescents with MetS, thus suggesting that even relatively short-term impairments in metabolism, in the absence of clinically manifest vascular disease, may give rise to brain complications. In view of these alarming results, it is plausible that obesity-associated metabolic disease, short of type 2 diabetes mellitus, may be mechanistically linked to lower the academic and professional potential of adolescents. Although obesity may not be enough to stir clinicians or even parents into action, these results in adolescents strongly argue for an early and comprehensive intervention. We propose that brain function be introduced among the parameters that need to be evaluated when considering early treatment of childhood obesity. Pediatrics 2012;130:e856-e864 As a result of the childhood obesity epidemic, in 2006, the prevalence of metabolic syndrome (MetS) was already 8.6% among all US children and adolescents. 1 MetS in childhood predicts MetS and type 2 diabetes mellitus (T2DM) in adulthood. 2 The MetS is composed of 5 obesity-associated components, namely elevations in fasting glucose levels or insulin resistance (IR) dependent on the definition used, 3,4 lower high-density lipoprotein (HDL), hypertriglyceridemia, and hypertension in addition to abdominal obesity. MetS among middle-aged and older adults has been associated with cognitive dysfunction. 5 However, to date, no brain data...

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Section: Discussionmentioning

confidence: 60%

“…6,7 Studying nondiabetic youth with MetS presents a unique opportunity to evaluate whether brain structure and function are affected by metabolic dysregulation of relatively short duration and before the development of hyperglycemia or clinically manifest cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

Obesity and Metabolic Syndrome and Functional and Structural Brain Impairments in Adolescence

Yau¹,

Castro²,

Tagani³

et al. 2012

Pediatrics

Self Cite

228

179

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“…Obesity is the greatest risk factor for insulin resistance, while mid-life obesity increases risk of Alzheimer's disease later in life [15]. In addition, obesity in adolescents is associated with cognitive deficits [16], suggesting that poor diet in early life reduces cognitive performance during the formative years.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin

et al. 2012

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Aims/hypothesis We previously demonstrated that animals fed a high-fat (HF) diet for 10 weeks developed insulin resistance and behavioural inflexibility. We hypothesised that intervention with metformin would diminish the HF-feedingevoked cognitive deficit by improving insulin sensitivity. Methods Rats were trained in an operant-based matching and non-matching to position task (MTP/NMTP). Animals received an HF (45% of kJ as lard; n024), standard chow (SC; n016), HF + metformin (144 mg/kg in diet; n020) or SC + metformin (144 mg/kg in diet; n016) diet for 10 weeks before retesting. Body weight and plasma glucose, insulin and leptin were measured. Protein lysates from various brain areas were analysed for alterations in intracellular signalling or production of synaptic proteins. Results HF-fed animals developed insulin resistance and an impairment in switching task contingency from matching to non-matching paradigm. Metformin attenuated the insulin resistance and weight gain associated with HF feeding, but had no effect on performance in either MTP or NMTP tasks. No major alteration in proteins associated with insulin signalling or synaptic function was detected in response to HF diet in the hypothalamus, hippocampus, striatum or cortex. Conclusions/interpretation Metformin prevented the metabolic but not cognitive alterations associated with HF feeding.The HF diet protocol did not change basal insulin signalling in the brain, suggesting that the brain did not develop insulin resistance. These findings indicate that HF diet has deleterious effects on neuronal function over and above those related to insulin resistance and suggest that weight loss may not be sufficient to reverse some damaging effects of poor diet.

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“…Altfas (34) reported that ADHD was highly prevalent among obese patients and highest in those with extreme obesity. Bruehl et al (35) reported that adolescents with type 2 DM with insulin resistance have significantly reduced hippocampal and prefrontal volumes and higher rates of global cerebral atrophy as compared with obese controls without insulin resistance. Insulin and insulin receptor signaling play a modulatory role in learning and memory processing (36).…”

Section: Discussionmentioning

confidence: 99%

Association of attention-deficit/hyperactivity disorder with diabetes: a population-based study

et al. 2013

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Background: cognitive impairment has been documented in adult diabetes but is unclear in pediatric diabetes. No study had been conducted to explore the relationship between attention-deficit/hyperactivity disorder (aDhD) and diabetes. Using a population-based data set, we aimed to examine the association between aDhD and a prior diagnosis of diabetes mellitus (DM) in Taiwan. Methods: a total of 4,302 patients with aDhD were selected as cases and 21,510 randomly selected subjects as controls. We used conditional logistic regression to calculate the odds ratio (OR) for having previously received a diagnosis of DM between subjects with and without aDhD. results: In this study, 116 of the 25,812 sampled subjects (0.5%) had received a diagnosis of DM prior to their index date. subjects with aDhD had a higher proportion of prior DM diagnoses than controls (0.9% vs. 0.4%, P < 0.001). after adjusting for age, sex, index year, geographic location, and obesity, aDhD was significantly associated with a prior diagnosis of type 2 DM (OR = 2.75, 95% confidence interval (cI) = 1.82-4.16). however, no significant association was observed between aDhD and type 1 DM. conclusion: The findings suggest that aDhD was associated with a previous diagnosis of type 2 DM.

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Obese Adolescents with Type 2 Diabetes Mellitus Have Hippocampal and Frontal Lobe Volume Reductions

Cited by 73 publications

References 50 publications

Obesity and Metabolic Syndrome and Functional and Structural Brain Impairments in Adolescence

Obesity and Metabolic Syndrome and Functional and Structural Brain Impairments in Adolescence

A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin

Association of attention-deficit/hyperactivity disorder with diabetes: a population-based study

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