Both type 1 and type 2 diabetes have been associated with reduced performance on multiple domains of cognitive function and with structural abnormalities in the brain. With an aging population and a growing epidemic of diabetes, central nervous system–related complications of diabetes are expected to rise and could have challenging future public health implications. In this review, we will discuss the brain structural and functional changes that have been associated with type 1 and type 2 diabetes. Diabetes duration and glycemic control may play important roles in the development of cognitive impairment in diabetes, but the exact underlying pathophysiological mechanisms causing these changes in cognition and structure are not well understood. Future research is needed to better understand the natural history and the underlying mechanisms, as well as to identify risk factors that predict who is at greatest risk of developing cognitive impairment. This information will lead to the development of new strategies to minimize the impact of diabetes on cognitive function.

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Background: The relation between malnutrition and pulmonary death in patients with cystic fibrosis (CF) has resulted in intensive nutritional intervention over the last few decades, leading to a significant decline in underweight and the emergence of overweight/obesity as a potential new problem. Methods: We performed a cross-sectional database analysis of 484 adults with CF seen at the University of Minnesota CF Center between January 2015-January 2017, to determine the prevalence and pulmonary/cardiovascular risk factors associated with overweight and obesity in this population. Results: Mean age was 35.2 ± 11.6 years. 5.2% were underweight (BMI < 18.5 kg/m 2), 62.6% normal weight (BMI ≥ 18.5-24.9 kg/m 2), 25.6% overweight (BMI ≥ 25-29.9 kg/m 2) and 6.6% obese (BMI ≥ 30 kg/m 2). In the subgroup with severe genotypes, 25% had BMI ≥ 25 kg/m 2. In the entire cohort, overweight/obese were likely to be older (OR = 1.04, p < 0.0 0 01) and to have a mild CFTR genotype (OR = 3.33, p = 0.0 0 03) and modestly elevated triglyceride levels (OR = 1.0 08, p < 0.0 0 01). The prevalence of hypertension was higher in overweight (25%) and obese (31%) than normal (17%) or underweight (16%), p = 0.01. Total cholesterol levels were higher in overweight/obese versus normal/underweight (144-147 vs 123-131 mg/dL, p = 0.04) as were LDL levels (70-71 vs 53-60 mg/dL, p = 0.02), but all were within the normal range. Percent predicted FEV1 was higher in overweight/obese (78-81%) versus underweight (59%) and normal (70%), p < 0.0 0 01, and overweight/obese experienced significantly fewer acute pulmonary exacerbations. Conclusions: Overweight/obesity is common in adults with CF including those with severe genotypes. Lung function is better in the overweight/obese and lipid levels are within the normal range, albeit higher than in normal/underweight.

The thalamus has been found to be activated during the early phase of moderate hypoglycemia. Here, we tested the hypothesis that this region is less activated during hypoglycemia in subjects with type 1 diabetes (T1DM) and hypoglycemia unawareness relative to controls. Twelve controls (5 F/7 M, age 40±14 years, body mass index 24.2±2.7 kg/m 2 ) and eleven patients (7 F/4 M, age 39 ± 13 years, body mass index 26.5 ± 4.4 kg/m 2 ) with well-controlled T1DM (A1c 6.8 ± 0.4%) underwent a two-step hyperinsulinemic (2.0 mU/kg per minute) clamp. Cerebral blood flow (CBF) weighted images were acquired using arterial spin labeling to monitor cerebral activation in the midbrain regions. Blood glucose was first held at 95 mg/dL and then allowed to decrease to 50 mg/dL. The CBF image acquisition during euglycemia and hypoglycemia began within a few minutes of when the target blood glucose values were reached. Hypoglycemia unaware T1DM subjects displayed blunting of the physiologic CBF increase that occurs in the thalamus of healthy individuals during the early phase of moderate hypoglycemia. A positive correlation was observed between thalamic response and epinephrine response to hypoglycemia, suggesting that this region may be involved in the coordination of the counter regulatory response to hypoglycemia.

summary Hippocampal dysfunction is known to be associated with several neurological and neuropsychiatric disorders such as Alzheimer's disease, epilepsy, schizophrenia and depression, therefore there has been significant clinical interest to study hippocampal neurochemistry. However the hippocampus is a challenging region to study using 1H MRS, hence the use of MRS for clinical research in this region has been limited. Therefore, our goal was to investigate the feasibility of obtaining high quality hippocampal spectra that allow reliable quantification of a neurochemical profile and to establish inter-session reproducibility of hippocampal MRS, including reproducibility of voxel placement, spectral quality and neurochemical concentrations. Ten healthy volunteers were scanned in two consequent sessions using a standard clinical 3T MR scanner. Neurochemical profiles were obtained with a short-echo (TE=28ms) semi-LASER localization sequence from a relatively small (~4mL) voxel that covered ~62% of the hippocampal volume as calculated from segmentation of T1-weighted images. Voxel composition was highly reproducible between sessions, with test-retest coefficients-of-variance (CV) of 3.5% and 7.5% for gray and white matter volume fraction, respectively. Excellent signal-to-noise ratio (~54 based on the N-acetylaspartate (NAA)-methyl peak in non-apodized spectra) and linewidths (~9 Hz for water) were achieved reproducibly in all subjects. The spectral quality allowed quantification of NAA, total choline, total creatine, myo-inositol and glutamate with high scan-rescan reproducibility (CV ≤ 6%) and quantification precision (Cramér-Rao lower bounds, CRLB < 9%). Four other metabolites, including glutathione and glucose, were quantified with scan-rescan CV below 20%. Therefore, the highly optimized, short echo semi-LASER sequence together with FASTMAP shimming substantially improved the reproducibility and number of quantifiable metabolites relative to prior reports. In addition, the between-session variation in metabolite concentrations, as well as CRLB were lower than between-subject variation of the concentrations for most metabolites indicating that the method has the sensitivity to detect inter-individual differences in the healthy brain.

BackgroundHypoglycemic episodes are infrequent in individuals without a history of diabetes mellitus or bariatric surgery. When hypoglycemia does occur in such individuals, an uncommon but important diagnosis to consider is non-islet cell tumor hypoglycemia (NICTH). We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature.Case presentationA 60 year old male with no relevant past medical history was referred to the endocrinology clinic with 18 month history of episodic hypoglycemic symptoms and, on one occasion was noted to have a fingerstick glucose of 36 mg/dL while having symptoms of hypoglycemia. Basic laboratory evaluation was unrevealing. Further evaluation however showed an elevated serum IGF-2 level at 2215 ng/mL (reference range 411–1248 ng/mL). Imaging demonstrated a large right suprarenal mass. A right nephrectomy with resection of the mass demonstrated a malignant solitary fibrous tumor. Post resection, the patient’s IGF-2 levels normalized and hypoglycemic symptoms resolved.ConclusionDue to the structural and biochemical homology between IGF-2 and insulin, elevated levels of IGF-2 can result in hypoglycemia. A posttranslational precursor to IGF-2 known as “big IGF” also possesses biologic activity. Review of recent reported cases of NICTH identified widespread anatomic locations and varied pathologic diagnoses of tumors associated with paraneoplastic production of IGF-2 causing hypoglycemia. Definitive management of hypoglycemia associated with paraneoplastic production of IGF-2 consists of resection of the tumor responsible for IGF-2 production. Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause.

In placebo-controlled trials of adult patients with or at high risk for type 2 DM, TZD therapy is significantly and consistently associated with a higher risk of HF. The risk of serious/severe HF is also increased with the use of TZDs. HF risks are similar to those of meta-analyses combining active- and placebo-controlled trials. The benefit/risk profile of TZDs should be considered when treating diabetic patients with or without prior HF.