Hypo and Hyper have qualitatively different effects on cognitive function in T1DM that depend in part on the timing of exposure during development, independent of onset age. This information extends the known benefits of avoiding both Hypo and chronic Hyper during childhood to include preservation of specific cognitive skills.

OBJECTIVE -Despite interest in the effects of type 1 diabetes on the developing brain, structural brain volumes in youth with this disease have not previously been examined. This study is the first to quantify regional brain volume differences in a large sample of youth with diabetes. RESEARCH DESIGN AND METHODS -Magnetic resonance images (MRIs)were acquired from youth with diabetes (n ϭ 108) and healthy sibling control subjects (n ϭ 51) aged 7-17 years. History of severe hypoglycemia was assessed by parent interview and included seizure, loss of consciousness, or requiring assistance to treat. A1C values since diagnosis were obtained from medical records; median A1C was weighted by duration of disease. Voxel-based morphometry was used to determine the relationships of prior hypo-and hyperglycemia to regional grey and white matter volumes across the whole brain.RESULTS -No significant differences were found between diabetic and healthy control groups in grey or white matter. However, within the diabetic group, a history of severe hypoglycemia was associated with smaller grey matter volume in the left superior temporal region. Greater exposure to hyperglycemia was associated with smaller grey matter volume in the right cuneus and precuneus, smaller white matter volume in a right posterior parietal region, and larger grey matter volume in a right prefrontal region.CONCLUSIONS -Qualitatively different relationships were found between hypo-and hyperglycemia and regional brain volumes in youth with type 1 diabetes. Future studies should investigate whether these differences relate to cognitive function and how these regions are affected by further exposure. Diabetes Care 30:2331-2337, 2007T ype 1 diabetes is known to have cumulative deleterious effects on the body, most notably on the retina, kidney, nerves, and blood vessels (1,2).The effects of diabetes on central nervous system structure and function are less well understood. A number of studies associate exposure to hypo-and hyperglycemia during childhood with deficits in specific cognitive domains (3,4). These findings suggest that during development, exposure to glycemic extremes may alter the structure or function of specific pathways or regions in the brain. Recent brain imaging studies in diabetic adults have reported differences in grey or white matter integrity associated with prior hypo-or hyperglycemia (5,6). However, the effects of diabetes on the developing brain have not been assessed in any largescale study to date (7). Assessing brain integrity earlier in the course of brain development and diabetes, followed by prospective monitoring, would be essential to determine when differences may emerge. Such knowledge could shed light on the neural basis of observed cognitive effects in children and adults with diabetes and determine whether there are developmental time periods during which the brain may be particularly vulnerable to the negative effects of hypoglycemia or hyperglycemia.The present study is the first to examine the structural integrity of t...

OBJECTIVEHippocampal neurons in adult animals and humans are vulnerable to severe hypoglycemia and hyperglycemia. Effects are hypothesized to be exacerbated during development, but existing studies on developing human brains are limited. We examined whether hypoglycemia or hyperglycemia experienced during brain development in humans affects hippocampal volumes.RESEARCH DESIGN AND METHODSWe analyzed T1-weighted magnetic resonance images in 95 youth with type 1 diabetes and 49 sibling control subjects aged 7–17 years. Youth with diabetes were categorized as having 0 (n = 37), 1–2 (n = 41), or 3 or more (3+; n = 17) prior severe hypoglycemic episodes. Hyperglycemia exposure was estimated from median lifetime A1C, weighted for duration of diabetes. Stereologic measurements of hippocampal volumes were performed in atlas-registered space to correct for whole brain volume.RESULTSGreater exposure to severe hypoglycemia was associated with larger hippocampal volumes (F [3,138] = 3.6, P = 0.016; 3+ larger than all other groups, P < 0.05). Hyperglycemia exposure was not associated with hippocampal volumes (R2 change = 0.003, F [1,89] = 0.31, P = 0.58, semipartial r = 0.06; one outlier removed for high median A1C), and the 3+ severe hypoglycemia group still had larger hippocampal volumes after controlling for age of onset and hyperglycemia exposure (main effect of hypoglycemia category, F [2,88] = 6.4, P = 0.002; 3+ larger than all other groups, P < 0.01).CONCLUSIONSEnlargement of the hippocampus may reflect a pathological reaction to hypoglycemia during brain development, such as gliosis, reactive neurogenesis, or disruption of normal developmental pruning.

Introduction The role of obesity in cardiovascular mortality is controversial. The obesity paradox has been widely attributed to smoking in the underweight. Large-scale studies analyzing the outcomes of peripheral arterial disease (PAD) in patients with a higher body mass index (BMI) while accounting for confounders such as smoking are lacking. Method The 2016 National Inpatient Sample (NIS) was used to identify all admissions with a primary discharge diagnosis of PAD. A secondary diagnosis of obesity or elevated BMI was used to segregate the admissions into two groups. Propensity scores were calculated to match and control both groups for age, smoking, and diabetes, amongst other confounders. A multivariate logistic and linear regression analysis was performed to calculate the odds ratio for in-hospital mortality, amputation, need for intervention (angioplasty or bypass), acute kidney injury, hospital charges, and length of stay. Non-obesity-related PAD admissions were selected as the reference groups. Results Among 248,288 PAD-related admissions, 41,618 had a secondary diagnosis of obesity. After calculating propensity scores for 1-1 matching, 41,589 admissions in the PAD and obesity group were compared to a similar number of admissions in the reference population. Patients with a concomitant diagnosis of obesity had lower odds of amputation (OR=0.90, 95% CI=0.84-0.95, p<0.001), need for intervention (OR=0.66, 95% CI=0.62-0.69, p<0.0001), and in-hospital mortality (OR=0.81, 95% CI=0.74-0.87, p<0.0001). On the contrary, the odds of having acute kidney injury were higher with elevated BMI (OR=1.30, 95% CI=1.26-1.34, p<0.0001). Conclusion Despite increasing the risk of hypertension, diabetes, and hypertriglyceridemia, the obesity paradox continues to exist with a better short-term prognosis in patients with PAD. Future studies looking into the pathophysiology behind this phenomenon are needed.

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