Decline in Beta-Cell Function among Adolescents with Type 2 Diabetes Mellitus

JMS SKIMS ◽  
2017 ◽  
Vol 20 (2) ◽  
pp. 115-116
Author(s):  
Shariq Rashid Masoodi
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Fasting Glucose ◽  
Newly Diagnosed ◽  
Annual Decline ◽  
Over Time

It is well known that beta-cell function declines over time in adults with type 2 diabetes mellitus (T2DM). The beta-cell dysfunction, initially characterized by impairment in the first phase of insulin secretion following glucose stimulation, advances to a decline in second phase insulin secretion as the disease progresses. But whether this decline in beta-cell function occurs in adolescents with T2DM is uncertain. Investigators prospectively compared beta-cell functioning over time between 39 adolescents with newly diagnosed T2DM (mean age, 15 years; body-mass index z-score, 2.4) and 32 obese adolescents without T2DM of comparable body-mass index, gender, and race (mean age, 14) during a 2-year period. Recently, researchers from Duke University School of Medicine, Durham North Carolina reported that adolescents with newly diagnosed T2DM had a 25% annual decline in beta-cell function despite receiving treatment. In this study, the results of which were first presented at the American Diabetes Association (ADA), the participants were adolescents with T2DM, more than half of whom were being treated with insulin whereas 80% were taking oral anti-diabetes medications. Beta-cell function in this study, assessed at baseline and 6, 12, and 24 months was measured by insulin secretion in response to an intravenous glucose load adjusted for insulin sensitivity (disposition index). The authors observed that adolescents with T2DM had significantly higher levels of both insulin resistance and fasting glucose at baseline compared with controls. But during the two-year study, the study subjects experienced a significant increase in fasting glucose and a 25 percent annual decline in disposition index. Understandably, both these indicators remained unchanged among the controls. JMS 2017;20(2):116

scholarly journals Effects of Liraglutide Combined with Short-Term Continuous Subcutaneous Insulin Infusion on Glycemic Control and Beta Cell Function in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Pilot Study

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Weijian Ke ◽  
Liehua Liu ◽  
Juan Liu ◽  
Ailing Chen ◽  
Wanping Deng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Continuous Subcutaneous Insulin Infusion ◽  
Insulin Infusion ◽  
Cell Function ◽  
Subcutaneous Insulin ◽  
Newly Diagnosed ◽  
Short Term

The objective of this paper is to investigate the effects of liraglutide in combination with short-term continuous subcutaneous insulin infusion (CSII) therapy on glycemic control and beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Thirty-nine eligible newly diagnosed T2DM patients were recruited and randomized to receive either of two therapies: short-term CSII alone (CSII alone group) or CSII in combination with liraglutide (CSII + Lira group) for 12 weeks. Blood glucose control, homeostasis model assessment (HOMA) indices, and acute insulin response (AIR) were compared between the two groups. The patients in CSII + Lira group achieved euglycemia with equivalent insulin dosage in shorter time (1 (0) versus 2 (3) days,P=0.039). HbA1c at the end of study was comparable between two groups (6.3±0.7% versus6.0±0.5%, for CSII alone group and CSII + Lira group, resp.,P=0.325). The increment of AIR was higher in CSII + Lira group (177.58 (351.57) μU·min/mL versus 58.15 (51.30) μU·min/mL,P<0.001). However, after stopping liraglutide, its effect on beta cell function disappeared completely. Liraglutide combined with short-term CSII was effective in further improving beta cell function, but the beneficial effects did not sustain after suspension of the therapy.

scholarly journals Relationship of Soluble RAGE with Insulin Resistance and Beta Cell Function during Development of Type 2 Diabetes Mellitus

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Subrata Kumar Biswas ◽  
Sabreena Mohtarin ◽  
Sonchita Rani Mudi ◽  
Taznuva Anwar ◽  
Laila Anjuman Banu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Newly Diagnosed ◽  
Control Subjects

This study examined whether circulating levels of soluble receptor for advanced glycation end products (sRAGE) alter in prediabetes and correlate with insulin resistance (IR) and beta cell function in prediabetes and newly diagnosed type 2 diabetes mellitus (T2DM). Subjects without previous history of diabetes were recruited and grouped as control, prediabetes, and newly diagnosed T2DM. The control subjects (n=40) and people with prediabetes (n=52) and diabetes (n=66) were similar in terms of age, sex, BMI, systolic and diastolic BP, and fasting insulin level. HOMA-IR was found significantly higher in people with diabetes than control subjects (p<0.001) and people with prediabetes (p=0.005); and HOMA-%B was found significantly deteriorated in people with diabetes (p<0.001) compared to control subjects and people with prediabetes. However, serum sRAGE levels did not show any significant alteration in people with prediabetes compared to control subjects. Moreover, univariate and multivariate analyses did not identify any significant correlation and statistical association of sRAGE with HOMA-IR and HOMA-%B in people with prediabetes and newly diagnosed T2DM. Our data suggest that serum sRAGE levels do not alter in people with prediabetes compared to control subjects and do not correlate or associate with IR and beta cell function during development of T2DM.

scholarly journals Clinical Significance of the Maximum Body Mass Index Before Onset of Type 2 Diabetes for Predicting Beta-Cell Function

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Harutoshi Ozawa ◽  
Kenji Fukui ◽  
Sho Komukai ◽  
Yoshiya Hosokawa ◽  
Yukari Fujita ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Clinical Significance ◽  
Beta Cell Function ◽  
Cell Function ◽  
Duration Of Diabetes ◽  
Maximum Body

Abstract Objective This study aimed to clarify the clinical significance of the maximum body mass index (BMI) before the onset of type 2 diabetes (MBBO) for predicting pancreatic beta-cell function. Methods This was a cross-sectional observational study. Of 1304 consecutively admitted patients with type 2 diabetes, we enrolled 410 patients satisfying the criteria in this study. The correlations between the C-peptide index (CPI), which is one of the parameters that reflects beta-cell function, and various clinical parameters, including MBBO and duration of diabetes, were analyzed in multiple linear regression analyses. Results The analyses revealed that MBBO was correlated with CPI independently after adjustment for age, sex, HbA1c, and duration of diabetes. When we divided the subjects into three subgroups by MBBO (MBBO &lt; 25 kg/m2; 25 kg/m2 ≤ MBBO &lt; 30 kg/m2; MBBO ≥ 30 kg/m2), CPI was negatively correlated with duration of diabetes in each subgroup, while the rates of CPI based on the duration of diabetes were not different among the three MBBO subgroups. In contrast, the declining rates of CPI were higher in the BMI ≥ 25 kg/m2 group on admission than in the BMI &lt; 25 kg/m2 group on admission. Conclusions MBBO may be an independent factor correlating with beta-cell function and may predict insulin secretion capacity at diagnosis, but it does not seem to affect the rate of decline in insulin secretion capacity after diagnosis. It is important to preserve beta-cell function by decreasing a patient’s BMI during treatment after diagnosis regardless of MBBO.

scholarly journals Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function

2015 ◽  
Vol 24 (10) ◽  
pp. 3004-3004 ◽  
Author(s):  
L. Shu ◽  
A. V. Matveyenko ◽  
J. Kerr-Conte ◽  
J.-H. Cho ◽  
C. H. S. McIntosh ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Protein Levels

scholarly journals Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function

2009 ◽  
Vol 18 (13) ◽  
pp. 2388-2399 ◽  
Author(s):  
Luan Shu ◽  
Aleksey V. Matveyenko ◽  
Julie Kerr-Conte ◽  
Jae-Hyoung Cho ◽  
Christopher H.S. McIntosh ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Protein Levels

scholarly journals SAT-667 Partial Beta-Cell Destruction: An Atypical Case of Immune Checkpoint Inhibitor Diabetes Mellitus

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Zoe Quandt ◽  
Katy K Tsai ◽  
Victoria C Hsiao
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Immune Checkpoint ◽  
Beta Cell Function ◽  
Cell Function ◽  
Autoimmune Diabetes ◽  
Insulin Production ◽  
C Peptide

Abstract Background: Autoimmune diabetes mellitus (CPI-DM) caused by immune checkpoint inhibitors (CPIs) is rare- occurring in approximately one percent of patients exposed to this form of cancer immunotherapy. Typically, this immune related adverse event occurs after treatment with PD-1/PD-L1 inhibitors. It is characterized by abrupt insulinopenia leading to acute hyperglycemia. Beta cell autoantibodies are positive in approximately half the cases. DKA is common at the time of diagnosis. Recovery of beta cell function has been reported in only two case reports. In one case, spontaneous resolution occurred following cessation of CPI therapy and in the other the patient was treated with infliximab for concurrent inflammatory arthritis prior to resolution of CPI-DM. Clinical Case: A 50-year-old woman was started on adjuvant pembrolizumab for stage IIIC melanoma following surgery. She had no prior history of diabetes mellitus, thyroid disease, or other autoimmune disease. Pre-infusion random blood glucoses (RBG) were 84 - 105 mg/dL. After 36 weeks, she developed hypothyroidism (TSH 17.5 (0.5-4.1 mIU/L), FT4 6 (10-18 ug/dL)) and started levothyroxine. Pembrolizumab was continued. For nine weeks following her diagnosis with CPI- hypothyroidism, her pre-infusion RBG ranged from 102-133. At 45 weeks (15 cycles) after initiating pembrolizumab, her RBG was 260. She was not on glucocorticoids and had no other signs of inflammation or stress. Pembrolizumab was continued. Just prior to her 17th cycle, 48 weeks after initiating adjuvant pembrolizumab, her RBG was 482 with a normal anion gap and HCO3, and her A1c was 8.9%. Her last dose of pembrolizumab was held. She started metformin and liraglutide. In just three weeks, a random c-peptide was inadequate at 1.7 (0.8-3.5 ng/mL) with a recent RBG of 220 and A1c of 10.3%, showing the acuity and extremity of her hyperglycemia. Over the course of the year, she has achieved excellent glucose control (A1c 6.3-7.1) on this regimen with preservation of insulin production (c-peptides 1.4-1.8 with matched RBG 92-129). She never required insulin. Her beta cell autoantibodies are negative. Clinical Lessons: This is a case of CPI-DM in which the patient did not have complete loss of beta-cell function. The acuity of her hyperglycemia is not consistent with new onset type 2 diabetes. At diagnosis, her c-peptide was inadequate suggesting insufficient insulin production rather than insulin resistance. Therefore, her hyperglycemia is more consistent with CPI-DM than type 2 diabetes. Atypically, she did not progress to fulminant beta cell failure, which could have been due to cessation of pembrolizumab (which is not unique to this case), initiation of liraglutide and metformin, or other unknown immunologic responses that inhibited full beta cell loss. This case raises the possibility of preventing fully insulin dependent CPI-DM if hyperglycemia is caught and treated early.

scholarly journals High Mobility Group Box 1 and Dickkopf-Related Protein 1 as New Biomarkers of Type 2 Diabetes Mellitus: Associations with Increased Glucose Toxicity and Atherogenicity and Lower β Cell Function

2020 ◽  
Author(s):  
Hussein Kadhem Al-Hakeim ◽  
Qasim Jasim Al-Kaabi ◽  
Michael Maes
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
High Mobility ◽  
Related Protein ◽  
Glucose Toxicity ◽  
Wnt Pathways

Background: Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to increased levels of high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). Objective: The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Methods: Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. Results: HMGB1 and DKK1 are significantly higher in T2DM irrespective of hypertension. T2DM was also accompanied by increased atherogenicity indices. HMGB1 and DKK1 are significantly correlated with HbA1c, glucose, indices of insulin resistance, &beta;-cell function, and glucose toxicity, and different atherogenic indices. A large part of the variance in the &beta;-cell index (30.5%) and glucose toxicity (34.8%) was explained by the combined effects of HMGB1 and DKK1 and hypertension. We found that 18.3% of the variance of the atherogenic index of plasma was explained by HMGB1 and DKK1 levels and that 31.2% was explained by glucose toxicity, HMGB1 and body weight. Conclusion: The higher serum HMGB1 and DKK1 levels in T2DM patients and the associations with atherogenicity indicate that low grade inflammation and disorders in the Wnt pathways are associated with T2DM and that both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in &beta;-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are new drug targets in the treatment of T2DM.

Sign in / Sign up

Export Citation Format

Share Document