Faculty Bibliography

OBJECTIVES: To determine the point prevalences of metabolic syndrome (MetS) and its components among healthy weight, overweight, and obese inner-city public high school students, to compare the prevalences of MetS when using 2 different definitions (one with the impaired fasting glucose [IFG] level and the other with a homeostasis model assessment of insulin resistance [HOMA-IR] of 3.99 or higher to define the glucose regulation component), and to compare the degree to which HOMA-IR and fasting glucose level are associated with the other MetS components. DESIGN: Cross-sectional analysis. SETTING: Two New York City public high schools, from April 2008 through August 2011. PARTICIPANTS: Convenience sample of 1185 high school youth, comprising predominantly Hispanic and African American students from low-income households, participating in The Banishing Obesity and Diabetes in Youth Project, a medical screening and education program. MAIN OUTCOME MEASURES: Prevalences of the following individual MetS components: IFG threshold, HOMA-IR, hypertension, central adiposity, hypertriglyceridemia, and low high-density lipoprotein cholesterol. Rates of MetSIFG and MetSHOMA-IR were also assessed. RESULTS: MetSIFG and MetSHOMA-IR point prevalences were both 0.3% in the healthy weight group; they were 2.6% and 5.9%, respectively, in the overweight group and were 22.9% and 35.1%, respectively, in the obese group (P < .05 for both). An IFG threshold of 100 mg/dL or higher was found in 1.0% of participants, whereas a HOMA-IR of 3.99 or higher was found in 19.5% of participants. CONCLUSIONS: An elevated HOMA-IR is much more sensitive than an IFG threshold in identifying adolescents with metabolic dysregulation. Using a HOMA-IR threshold of 3.99 identifies more youth with MetS than using an IFG threshold of 100 mg/dL. In addition to increasing the sensitivity of MetS detection, HOMA-IR has a much higher association with the other MetS components than the IFG threshold and may better reflect a unified underlying pathologic process useful to identify youth at risk for disease.

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.

Metabolic syndrome (MetS), a clustering of risk factors for type 2 diabetes mellitus and cardiovascular disease, has been associated with cognitive dysfunction and brain abnormalities. This review describes the literature on the impact of MetS on brain and cognition and suggests directions for future research. A literature search for reports of MetS and cognition and brain imaging was conducted for both nonelderly adults and adolescents. No studies were found describing MetS and brain or cognition among adolescents; therefore, we also included studies investigating individual components of MetS in this age group. Most studies found associations between MetS and cognitive dysfunction. Multiple cognitive domains were affected by MetS in adults. In adolescents, the majority of findings were in executive functioning. Brain imaging literature in adults implicated MetS in ischemic stroke, white matter alterations, and altered brain metabolism. For adolescents, individual MetS factors were linked to volume losses in the hippocampus and frontal lobes. MetS negatively impacts cognitive performance and brain structure. Potential explanatory models include impaired vascular reactivity, neuroinflammation, oxidative stress, and abnormal brain lipid metabolism. We posit that insulin resistance-associated impairment in cerebrovascular reactivity is an important mechanism underlying brain deficits seen in MetS.

Recent studies have demonstrated alterations in the cortisol awakening response (CAR) and brain abnormalities in adults with obesity and type 2 diabetes mellitus (T2DM). While adolescents with T2DM exhibit similar brain abnormalities, less is known about whether brain impairments and hypothalamic-pituitary-adrenal (HPA) axis abnormalities are already present in adolescents with pre-diabetic conditions such as insulin resistance (IR). This study included 33 adolescents with IR and 20 without IR. Adolescents with IR had a blunted CAR, smaller hippocampal volumes, and greater frontal lobe atrophy compared to controls. Mediation analyses indicated pathways whereby a smaller CAR was associated with higher BMI which was in turn associated with fasting insulin levels, which in turn was related to smaller hippocampal volume and greater frontal lobe atrophy. While we had hypothesized that HPA dysregulation may result from brain abnormalities, our findings suggest that HPA dysregulation may also impact brain structures through associations with metabolic abnormalities.

OBJECTIVE: Studies of behavioral weight loss intervention in patients with psychotic disorders are sparse, and its efficacy compared to other obese patients is unknown. Therefore, we compared the effect of a cognitive-behavioral weight loss intervention in obese subjects with psychotic disorders, other psychiatric diagnoses, and without psychiatric disorders. METHODS: A 12-month naturalistic study of weekly group or individual cognitive-behavioral weight management in 222 consecutively enrolled obese patients (body mass index [BMI], 43.7 +/- 9.6 kg/m) with psychotic spectrum disorders (PSDs, n = 47), other psychiatric disorders (OPDs, n = 49), and no psychiatric disorder (NPD, n = 126). RESULTS: Patients with PSD had greater treatment persistence (48.9%) and longer treatment duration (8.7 +/- 4.4 months) than those with OPD (22.4% and 5.4 +/- 4.3 months) and NPD (22.2% and 4.9 +/- 4.7 months) (P < 0.01 for all; number needed to treat, 3). In last-observation-carried-forward analyses, patients with PSD had greater percent baseline weight loss at 12 months (5.1% +/- 9.3%) than patients with OPD and with NPD (2.7% +/- 5.5% and 2.4% +/- 6.3%); greater percent BMI loss at 9 and 12 months than both groups (P < 0.05 for all) and greater BMI loss at 9 months (2.1 +/- 3.5 kg/m) and 12 months (2.3 +/- 4.1 kg/m) than NPD patients (1.1 +/- 2.3 and 1.2 +/- 2.4 kg/m). Furthermore, weight loss of 5% or more occurred in 42.6% of patients with PSD versus 18.4% and 23.0% in OPD and NPD patients (P < 0.01 for all; numbers needed to treat, 5 and 6). The strongest weight loss predictor was treatment duration (beta = 0.51-0.54; P < 0.001). Attrition was predicted by NPD (P = 0.001) and OPD group status (P = 0.036), lower proportion of group sessions (P = 0.002), higher depression (P = 0.028), and lower baseline BMI (P = 0.030). CONCLUSIONS: Patients with PSD had greater weight loss than other obese patients. Nonadherence and depression should be targeted to enhance weight loss success.

ABSTRACT: BACKGROUND: To ascertain whether the associations between obesity, inflammation, and insulin resistance established in human adult studies are found among adolescents. METHODS: We contrasted 36 obese and 24 lean youth on fasting glucose, insulin levels, lipid profile, hemoglobin A1C, markers of hepatic function, white blood cell count, C-reactive protein (CRP) and fibrinogen levels. The cytokines IL-6, TNF-alpha, IFN-gamma, IL-10 and IL-4 and the adipokines leptin, resistin, and adiponectin were also compared between the two groups. The fasting glucose and insulin values were used to estimate the degree of insulin resistance with the homeostatic model assessment of insulin resistance (HOMA-IR). T-tests and correlations were run to examine group differences and associations between groups. In addition, regression analyses were used to ascertain whether the markers of inflammation were predictive of the degree of insulin resistance. RESULTS: Although obese adolescents had clear evidence of insulin resistance, only CRP, fibrinogen and leptin were elevated; there were no group differences in pro- or anti-inflammatory cytokines nor adiponectin and resistin. Anthropometric measures of obesity and level of insulin resistance were highly correlated to the acute phase reactants CRP and fibrinogen; however, the degree of insulin resistance was not predicted by the pro- or anti-inflammatory cytokine markers. Obese adolescents had higher white blood cell counts. In addition they had higher circulating alanine aminotransferase concentrations and lower circulating albumin and total protein than lean adolescents, possibly as a result of hepatocyte damage from fatty liver. CONCLUSION: Unlike rodent or adult studies, we found that wide-spread systemic inflammation is not necessarily associated with insulin resistance among adolescents. This finding does not support the current paradigm that the associations between obesity and insulin resistance are, to a significant degree, mediated by low grade systemic inflammation. These data support the need for further adolescent studies to explore these associations.

Type 2 diabetes (T2DM) and cardiovascular disease (CVD) are rising dramatically in adolescents in parallel with excess weight. The Banishing Obesity and Diabetes in Youth (BODY) Project, is a school-based intervention that medically screens overweight and obese high school students, provides personalized feedback, and connects to appropriate healthcare. Body mass index (BMI) was determined for 1,526 students in one New York City public high school with a school-based health center (SBHC). Overweight and obese students (n = 640) were invited to complete a medical evaluation that included a survey, blood pressure and blood tests. 328/640 (51%) eligible students returned signed parental consent and participated. All participants received a personalized report detailing their results along with specific recommendations on how to improve their health. Parents of participants with results outside healthy ranges (82%; 270/328) were called and mailed referral letters to connect with healthcare services. Project staff reached by telephone 74% (199/270) of those families and 29% (58/199) stated that the report led them to make arrangements to see a healthcare provider. Most students (83%; 273/328) were registered at the SBHC, and we shared their medical results with them so they could follow-up with the students. The BODY Project is a feasible program for urban schools with a SBHC. This may allow effective prevention of T2DM, and CVD from dyslipidemia and hypertension.

Hypothalamic-pituitary-adrenal (HPA) axis control may be impaired in type 2 diabetes (T2DM). Glucocorticoids increase consumption of low quality foods high in calories, sugar, and fat. We explored the relationship between cortisol levels, poor blood glucose control, and food quality choice in T2DM. Twenty-seven healthy controls were age-, gender- and education-matched to 27 T2DM participants. Standard clinical blood tests and cortisol values were measured from fasting blood samples. Participants recorded all consumed food and drink items in a consecutive 3-day food diary. Diaries were analyzed for 'high quality' and 'low quality' foods using a standardized method with high reliability (0.97 and 0.86, respectively). Controlling for education, body mass index (BMI) and hemoglobin A1C (HbA1C), log-transformed cortisol (LogC) predicted the percent of low quality foods (R (2) = 0.092, beta = 0.360, P < 0.05), but not the percent of high quality foods chosen. Controlling for education, BMI, and LogC, HbA1C significantly predicted both the percent of low quality foods (DeltaR (2) = 0.079, beta = 0.348, P = 0.024) and high quality foods chosen (DeltaR (2) = 0.085, beta = -0.362, P = 0.022). The relationship between HbA1C and low quality food choice may be mediated by cortisol, controlling for BMI and education (P < 0.01). HbA1C displayed both an indirect (cortisol-mediated) effect (P < 0.05) and direct effect on low quality food choice (P < 0.05). The relationship between HbA1C and low quality food choice may be partially mediated by cortisol. Poor blood glucose control may cause HPA axis disruption, increased consumption of low quality foods

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been shown to result in medical complications on several organ systems including the kidneys, eyes, cardiovascular system, and most recently described the brain, including the hippocampus. There is also evidence that females are disproportionately affected by these medical complications. Brain volume reductions have also been associated with chronic low-grade inflammation and dyslipidaemia. This study investigated the relationships among T2DM, gender, inflammation, dyslipidaemia, and hippocampal volumes. METHOD: Participant groups consisted of 40 obese adults with T2DM and 47 lean adults, group-matched on age, gender, race, and education. Each participant underwent medical examination including a standard panel of blood tests, a magnetic resonance imaging, and cognitive evaluation. RESULTS: We show that there is a gender difference in the association of T2DM and hippocampal volumes: diabetic women are most affected despite having better glucose control than their male counterparts. Although females with T2DM had disproportionately lower high density lipoprotein as well as better haemoglobin A1c, neither of these results explained why females with T2DM had the smallest hippocampal volumes. CONCLUSIONS: These important findings indicate that in addition to the higher rate of traditional medical complication, females with T2DM are likely to suffer more brain complications than males. These observations, if supported by larger studies, suggest that in the future gender could be considered when customizing diabetes treatment.