scholarly journals Evidence That Hypothalamic Gliosis Is Related to Impaired Glucose Homeostasis in Adults With Obesity

2021 ◽  
Author(s):  
Jennifer L. Rosenbaum ◽  
Susan J. Melhorn ◽  
Stefan Schoen ◽  
Mary F. Webb ◽  
Mary Rosalynn B. De Leon ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Relaxation Times ◽  
Normal Glucose Tolerance ◽  
T2 Relaxation ◽  
Β Cell ◽  
Normal Glucose

Objective: Preclinical research implicates hypothalamic glial cell responses in the pathogenesis of obesity and type 2 diabetes. The current study sought to translate such findings into humans by testing if radiologic markers of gliosis in the mediobasal hypothalamus (MBH) were greater in persons with obesity and impaired glucose homeostasis or type 2 diabetes. <p>Research Design and Methods: Using cross-sectional and prospective cohort study designs, we applied a validated, quantitative magnetic resonance imaging (MRI) approach to assess gliosis in 67 adults with obesity and normal glucose tolerance, impaired glucose tolerance, or type 2 diabetes. Assessments of glucose homeostasis were conducted via oral glucose tolerance tests (OGTT) and β-cell modeling. </p> <p> Results: We found significantly greater T2 relaxation times (a marker of gliosis by MRI), that were independent of adiposity, in the impaired glucose tolerance and type 2 diabetes groups as compared to the normal glucose tolerance group. Findings were present in the MBH, but not control regions. Moreover, positive linear associations were present in the MBH but not control regions between T2 relaxation time and glucose area under the curve during an OGTT, fasting glucose concentrations, hemoglobin A1c, and visceral adipose tissue mass, whereas negative linear relationships were present in the MBH for markers of insulin sensitivity and β-cell function. In a prospective cohort study, greater MBH T2 relaxation times predicted declining insulin sensitivity over one year. </p> Conclusions: Findings support a role for hypothalamic gliosis in the progression of insulin resistance in obesity and, thus, type 2 diabetes pathogenesis in humans.

scholarly journals Evidence That Hypothalamic Gliosis Is Related to Impaired Glucose Homeostasis in Adults With Obesity

2021 ◽  
Author(s):  
Jennifer L. Rosenbaum ◽  
Susan J. Melhorn ◽  
Stefan Schoen ◽  
Mary F. Webb ◽  
Mary Rosalynn B. De Leon ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Relaxation Times ◽  
Normal Glucose Tolerance ◽  
T2 Relaxation ◽  
Β Cell ◽  
Normal Glucose

Objective: Preclinical research implicates hypothalamic glial cell responses in the pathogenesis of obesity and type 2 diabetes. The current study sought to translate such findings into humans by testing if radiologic markers of gliosis in the mediobasal hypothalamus (MBH) were greater in persons with obesity and impaired glucose homeostasis or type 2 diabetes. <p>Research Design and Methods: Using cross-sectional and prospective cohort study designs, we applied a validated, quantitative magnetic resonance imaging (MRI) approach to assess gliosis in 67 adults with obesity and normal glucose tolerance, impaired glucose tolerance, or type 2 diabetes. Assessments of glucose homeostasis were conducted via oral glucose tolerance tests (OGTT) and β-cell modeling. </p> <p> Results: We found significantly greater T2 relaxation times (a marker of gliosis by MRI), that were independent of adiposity, in the impaired glucose tolerance and type 2 diabetes groups as compared to the normal glucose tolerance group. Findings were present in the MBH, but not control regions. Moreover, positive linear associations were present in the MBH but not control regions between T2 relaxation time and glucose area under the curve during an OGTT, fasting glucose concentrations, hemoglobin A1c, and visceral adipose tissue mass, whereas negative linear relationships were present in the MBH for markers of insulin sensitivity and β-cell function. In a prospective cohort study, greater MBH T2 relaxation times predicted declining insulin sensitivity over one year. </p> Conclusions: Findings support a role for hypothalamic gliosis in the progression of insulin resistance in obesity and, thus, type 2 diabetes pathogenesis in humans.

Liraglutide Therapy in a Prediabetic State: Rethinking the Evidence

2020 ◽  
Vol 16 (7) ◽  
pp. 699-715 ◽  
Author(s):  
Georgios S. Papaetis
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Normal Glucose Tolerance ◽  
Current Evidence ◽  
Β Cell ◽  
Prediabetic State ◽  
New Therapeutic Approaches ◽  
Normal Glucose

Background: Prediabetes is defined as a state of glucose metabolism between normal glucose tolerance and type 2 diabetes. Continuous β-cell failure and death are the reasons for the evolution from normal glucose tolerance to prediabetes and finally type 2 diabetes. Introduction: The necessity of new therapeutic approaches in order to prevent or delay the development of type 2 diabetes is obligatory. Liraglutide, a long-acting GLP-1 receptor agonist, has 97% homology for native GLP-1. Identification of the trophic and antiapoptotic properties of liraglutide in preclinical studies, together with evidence of sustained β-cell function longevity during its administration in type 2 diabetes individuals, indicated its earliest possible administration during this disease, or even before its development, so as to postpone or delay its onset. Methods: Pubmed and Google databases have been thoroughly searched and relevant studies were selected. Results: This paper explores the current evidence of liraglutide administration both in humans and animal models with prediabetes. Also, it investigates the safety profile of liraglutide treatment and its future role to postpone or delay the evolution of type 2 diabetes. Conclusion: Liralgutide remains a valuable tool in our therapeutic armamentarium for individuals who are overweight or obese and have prediabetes. Future well designed studies will give valuable information that will help clinicians to stratify individuals who will derive the most benefit from this agent, achieving targeted therapeutic strategies.

Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance

2012 ◽  
Vol 303 (1) ◽  
pp. E122-E131 ◽  
Author(s):  
N. B. Jørgensen ◽  
S. H. Jacobsen ◽  
C. Dirksen ◽  
K. N. Bojsen-Møller ◽  
L. Naver ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Normal Glucose Tolerance ◽  
Long Term Effects ◽  
Β Cell ◽  
Liquid Meal ◽  
Normal Glucose

Our aim was to study the potential mechanisms responsible for the improvement in glucose control in Type 2 diabetes (T2D) within days after Roux-en-Y gastric bypass (RYGB). Thirteen obese subjects with T2D and twelve matched subjects with normal glucose tolerance (NGT) were examined during a liquid meal before (Pre), 1 wk, 3 mo, and 1 yr after RYGB. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent-insulinotropic polypeptide (GIP), and glucagon concentrations were measured. Insulin resistance (HOMA-IR), β-cell glucose sensitivity (β-GS), and disposition index (Dβ-GS: β-GS × 1/HOMA-IR) were calculated. Within the first week after RYGB, fasting glucose [T2D Pre: 8.8 ± 2.3, 1 wk: 7.0 ± 1.2 ( P < 0.001)], and insulin concentrations decreased significantly in both groups. At 129 min, glucose concentrations decreased in T2D [Pre: 11.4 ± 3, 1 wk: 8.2 ± 2 ( P = 0.003)] but not in NGT. HOMA-IR decreased by 50% in both groups. β-GS increased in T2D [Pre: 1.03 ± 0.49, 1 wk: 1.70 ± 1.2, ( P = 0.012)] but did not change in NGT. The increase in DIβ-GS was 3-fold in T2D and 1.5-fold in NGT. After RYGB, glucagon secretion was increased in response to the meal. GIP secretion was unchanged, while GLP-1 secretion increased more than 10-fold in both groups. The changes induced by RYGB were sustained or further enhanced 3 mo and 1 yr after surgery. Improvement in glycemic control in T2D after RYGB occurs within days after surgery and is associated with increased insulin sensitivity and improved β-cell function, the latter of which may be explained by dramatic increases in GLP-1 secretion.

Effect of High ß-Glucan Barley on Postprandial Plasma Glucose Levels in Subjects with Normal Glucose Tolerance and Patients with Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 772-P
Author(s):  
MARIKO HIGA ◽  
AYANA HASHIMOTO ◽  
MOE HAYASAKA ◽  
MAI HIJIKATA ◽  
AYAMI UEDA ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Normal Glucose Tolerance ◽  
Postprandial Plasma Glucose ◽  
Glucose Levels ◽  
Normal Glucose

Plasma Folate Levels in Men with Type 2 Diabetes

2005 ◽  
Vol 75 (5) ◽  
pp. 307-311
Author(s):  
Sakuta ◽  
Suzuki ◽  
Yasuda ◽  
Ito
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Vegetable Intake ◽  
Normal Glucose Tolerance ◽  
Diabetic Patients ◽  
Newly Diagnosed ◽  
Plasma Folate ◽  
Normal Glucose ◽  
Diagnosed Diabetes

Limited data suggest that folate levels are higher in patients with type 2 diabetes than in subjects with normal glucose tolerance (NGT). We compared the fasting plasma folate, glucose (FPG), body mass index (BMI), and supplementary vitamin use among male subjects with NGT, those with impaired glucose tolerance (IGT), those with newly diagnosed type 2 diabetes, and those with previously diagnosed type 2 diabetes. Plasma folate of patients with newly diagnosed diabetes and that of patients with previously diagnosed diabetes was significantly higher than that of NGT subjects (p < 0.001). Prevalence of vitamin use was lower in newly diagnosed or previously diagnosed diabetic patients compared with non-diabetic subjects. Self-rated vegetable intake was similar among the four groups. FPG, BMI, triglycerides, and systolic blood pressure correlated with plasma folate levels independently of lifestyle factors studied. These results suggest that plasma folate levels are elevated in male diabetic patients independently of health-conscious behavior that is recommended for diabetic people.

scholarly journals Changes in Glucose Tolerance over Time in Women with Polycystic Ovary Syndrome: A Controlled Study

2005 ◽  
Vol 90 (6) ◽  
pp. 3236-3242 ◽  
Author(s):  
Richard S. Legro ◽  
Carol L. Gnatuk ◽  
Allen R. Kunselman ◽  
Andrea Dunaif
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Polycystic Ovary ◽  
Normal Glucose Tolerance ◽  
Ovary Syndrome ◽  
Normal Glucose ◽  
Pcos Group ◽  
Over Time

We performed this study to access the changes in glucose tolerance over time in a group of women with polycystic ovary syndrome (PCOS) (n = 71) and control women (n = 23) with regular menstrual cycles and baseline normal glucose tolerance. Mean follow-up was between 2 and 3 yr for both groups (PCOS 2.5 ± 1.7 yr; controls 2.9 ± 2.1 yr). Based on World Health Organization glucose tolerance categories, there was no significant difference in the prevalence of glucose intolerance at follow-up in the PCOS group. In the PCOS group, 25 (37%) had impaired glucose tolerance (IGT) and seven (10%) had type 2 diabetes mellitus at baseline, compared with 30 (45%) and 10 (15%), respectively, at follow-up. There were also no differences within groups (PCOS or control) or between groups (PCOS vs. control) in the oral glucose tolerance test-derived measure of insulin sensitivity, but in the women with PCOS who converted to either IGT or type 2 diabetes mellitus, there was a significant decrease (P &lt; 0.0001). At the follow-up visit, the mean glycohemoglobin level was 6.1 ± 0.9% in women with PCOS vs. 5.3 ± 0.7% in the control women (P &lt; 0.001). Women with PCOS and baseline IGT had a low conversion risk of 6% to type 2 diabetes over approximately 3 yr, or 2% per year. The effect of PCOS, given normal glucose tolerance (NGT) at baseline, is more pronounced with 16% conversion to IGT per year. Our study supports that women with PCOS (especially with NGT) should be periodically rescreened for diabetes due to worsening glucose intolerance over time, but this interval may be over several years and not annually.

scholarly journals Serum IL-6 and sIL-6R in type 2 diabetes contribute to impaired capillary-like network formation

2019 ◽  
Vol 127 (2) ◽  
pp. 385-392
Author(s):  
Rian Q. Landers-Ramos ◽  
Jacob B. Blumenthal ◽  
Steven J. Prior
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Glucose Tolerance ◽  
Interleukin 6 ◽  
Network Formation ◽  
Normal Glucose Tolerance ◽  
Normal Glucose

We hypothesized that the serum from individuals with type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT) would reduce in vitro capillary-like network formation compared with normal glucose tolerance (NGT) serum and that this would occur along with higher serum concentrations of inflammatory cytokines and lower concentrations of angiogenic growth factors. Subjects were sedentary, older (55–65 yr) adults with NGT, IGT, or T2DM ( n = 10/group) matched for body mass index. Human retroviral telomerized endothelial cells (HRVT-ECs) or coronary artery endothelial cells (CECs) were used in a capillary-like network formation assay using endothelial basal medium supplemented with 7.5% serum. Quantification of HRVT-EC network length indicated that serum from the T2DM group resulted in 32 and 35% lower network formation than when using serum from the NGT and IGT groups, respectively ( P < 0.05). Serum from T2DM subjects resulted in CEC network formation that was 11 and 8% lower than when using serum from NGT and IGT subjects, respectively ( P < 0.05). Analysis of serum cytokines indicated that IL-6 was 41% and 49% higher in the IGT and T2DM groups, respectively, compared with the NGT group ( P < 0.05) and there was a trend for higher soluble interleukin-6 receptor (sIL-6R; P = 0.06) and IL-8 ( P = 0.08) in the T2DM serum compared with NGT. The use of recombinant IL-6 and sIL-6R at concentrations detected in the T2DM serum also reduced capillary network formation compared with NGT concentrations ( P < 0.05). These results suggest that IL-6 and sIL-6R present in the serum of T2DM individuals impair in vitro endothelial cell function across different cell lines. Our findings may have implications for the microvascular complications associated with T2DM. NEW & NOTEWORTHY Higher concentrations of serum factors, specifically Interleukin-6 and its soluble receptor found in individuals with type 2 diabetes (T2DM) appear to impair endothelial cell capillary-like network formation compared with those present in serum from individuals with impaired glucose tolerance and normal glucose tolerance. This may have implications for the vascular complications associated with T2DM.

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