People with Impaired Glucose Tolerance and Impaired Fasting Glucose Are Similarly Susceptible to Cardiovascular Disease: A Study in First-Degree Relatives of Type 2 Diabetic Patients

AbstractInterleukin-6 (IL6) is critically involved in inflammation and metabolism. About 1% of people produce IL6 autoantibodies (aAb-IL6) that impair IL6 signaling in vivo. We tested the hypothesis that the prevalence of such aAb-IL6 is increased in type 2 diabetic patients and that aAb-IL6 plays a direct role in causing hyperglycemia. In humans, the prevalence of circulating high-affinity neutralizing aAb-IL6 was 2.5% in the type 2 diabetic patients and 1% in the controls (odds ratio 2.5, 95% confidence interval 1.2–4.9, P=0.01). To test for the role of aAb-IL6 in causing hyperglycemia, such aAb-IL6 were induced in mice by a validated vaccination procedure. Mice with plasma levels of aAb-IL6 similar to the 2.5% type 2 diabetic patients developed obesity and impaired glucose tolerance (area under the curve (AUC) glucose, 2056±62 vs 1793±62, P=0.05) as compared with sham-vaccinated mice, when challenged with a high-fat diet. Mice with very high plasma levels of aAb-IL6 developed elevated fasting plasma glucose (mM, 4.8±0.4 vs 3.3±0.1, P<0.001) and impaired glucose tolerance (AUC glucose, 1340±38 vs 916±25, P<0.001) as compared with sham-control mice on normal chow. In conclusion, the prevalence of plasma aAb-IL6 at levels known to impair IL6 signaling in vivo is increased 2.5-fold in people with type 2 diabetes. In mice, matching levels of aAb-IL6 cause obesity and hyperglycemia. These data suggest that a small subset of type 2 diabetes may in part evolve from an autoimmune attack against IL6.

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Low-Dose Acrolein, an Endogenous and Exogenous Toxic Molecule, Inhibits Glucose Transport via an Inhibition of Akt-Regulated GLUT4 Signaling in Skeletal Muscle Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22137228 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7228

Author(s):

Ching-Chia Wang ◽

Huang-Jen Chen ◽

Ding-Cheng Chan ◽

Chen-Yuan Chiu ◽

Shing-Hwa Liu ◽

...

Keyword(s):

Skeletal Muscle ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Protein Expression ◽

Glucose Uptake ◽

Glucose Transport ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Type 2 Diabetic

Urinary acrolein adduct levels have been reported to be increased in both habitual smokers and type-2 diabetic patients. The impairment of glucose transport in skeletal muscles is a major factor responsible for glucose uptake reduction in type-2 diabetic patients. The effect of acrolein on glucose metabolism in skeletal muscle remains unclear. Here, we investigated whether acrolein affects muscular glucose metabolism in vitro and glucose tolerance in vivo. Exposure of mice to acrolein (2.5 and 5 mg/kg/day) for 4 weeks substantially increased fasting blood glucose and impaired glucose tolerance. The glucose transporter-4 (GLUT4) protein expression was significantly decreased in soleus muscles of acrolein-treated mice. The glucose uptake was significantly decreased in differentiated C2C12 myotubes treated with a non-cytotoxic dose of acrolein (1 μM) for 24 and 72 h. Acrolein (0.5–2 μM) also significantly decreased the GLUT4 expression in myotubes. Acrolein suppressed the phosphorylation of glucose metabolic signals IRS1, Akt, mTOR, p70S6K, and GSK3α/β. Over-expression of constitutive activation of Akt reversed the inhibitory effects of acrolein on GLUT4 protein expression and glucose uptake in myotubes. These results suggest that acrolein at doses relevant to human exposure dysregulates glucose metabolism in skeletal muscle cells and impairs glucose tolerance in mice.

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Incidence Rates of Type 2 Diabetes in People With Impaired Fasting Glucose (ADA vs. WHO Criteria) and Impaired Glucose Tolerance: Results From an Older Population (KORA S4/F4/FF4 Study)

Diabetes Care ◽

10.2337/dc18-1473 ◽

2018 ◽

Vol 42 (2) ◽

pp. e18-e20 ◽

Cited By ~ 3

Author(s):

Bernd Kowall ◽

Wolfgang Rathmann ◽

Brenda Bongaerts ◽

Oliver Kuss ◽

Andreas Stang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Impaired Fasting Glucose ◽

Fasting Glucose ◽

Incidence Rates ◽

Older Population ◽

Who Criteria

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Prevalence of newly diagnosed prediabetes, diabetes mellitus among the officers from Phuoc Long district of Binh Phuoc province

Vietnam Journal of Diabetes and Endocrinology ◽

10.47122/vjde.2020.40.4 ◽

2021 ◽

pp. 24-28

Author(s):

Thanh Long Le ◽

Trung Vinh Hoang

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Impaired Fasting Glucose ◽

Fasting Glucose ◽

Newly Diagnosed ◽

Personal Communications

Objective: To evaluate the prevalence of newly diagnosed prediabetes, diabetes mellitus among the officers from Phuoc Long district of Binh Phuoc province. Subjects and methods: 268 personals communications service was examined the impaired fasting glucose (G0); impaired glucose tolerance (G2) anh HbA1c. Results: Prevalence of prediabetes, type 2 diabetes mellitus by G0, G2, HbA1c as follows 16,0%; 13,1%; 17,9% and 3,8%; 6,7%; 2,2%. Common prevalence of prediabetes in 26,9%; type 2 diabetes mellitus in 7,1%. Conclusion: Personal communications service from Phuoc Long district have percentage of prediabetes higher compared to type 2 diabetes mellitus which of prediabetes was diagnosed by HbA1c which takes up the highest percentage; diabetes mellitus was diagnosed by G2which takes up the highest percentage.

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