Circulating mesencephalic astrocyte-derived neurotrophic factor is increased in newly diagnosed prediabetic and diabetic patients, and is associated with insulin resistance.

Evidence has shown that endoplasmic reticulum (ER) stress was involved in the progression to type 2 diabetes mellitus (T2DM) and development of insulin resistance. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel secreted protein upregulated by ER stress. This study aimed to assess serum level of MANF in normal glucose tolerance (NGT) participants and newly diagnosed prediabetic and T2DM patients. A total of 257 participants with NGT, newly diagnosed prediabetes or T2DM were recruited from Yinchao and Hangtian communities of Chengdu, Sichuan, China. Serum MANF level was quantified by enzyme-linked immunosorbent assay (ELISA). The mean age for the 257 participants (147 females) was 62±8 years (range 44-78): 71 with NGT, 115 with newly diagnosed prediabetes and 71 with T2DM. Mean serum MANF level was significantly higher with newly diagnosed prediabetes and T2DM than NGT (2.89±1.09 and 3.03±1.73 vs 2.13±1.37 ng/mL, both p<0.001). MANF level was not correlated with insulin sensitivity indexes (homeostasis model assessment for insulin resistance [HOMA-IR], Matsuda Index and quantitative insulin sensitivity check index [QUICKI]) for NGT and T2DM participants but was correlated with such indexes for prediabetes patients. We concluded that serum MANF level was higher in patients with newly diagnosed prediabetes and T2DM than in NGT controls. MANF appears to be associated with Matsuda Index, QUICKI and HOMA-IR in prediabetes patients.

Increased acyl ghrelin but decreased total ghrelin and unacyl ghrelin in Chinese Han people with impaired fasting glucose combined with impaired glucose tolerance.

We assessed the plasma acyl ghrelin (AG), unacyl ghrelin (UAG), and total ghrelin (TGhr) levels in Chinese adults with pre-diabetes and newly diagnosed diabetes mellitus (NDDM) after an oral glucose tolerance test (OGTT), and abdominal subcutaneous fat area and visceral fat area (VFA) were measured. Fasting AG level was increased in the impaired fasting glucose (IFG) combined with impaired glucose tolerance (IFG+IGT) and NDDM groups. AG, UAG, and TGhr levels were significantly decreased post-OGTT, and the decrements of 30-min AG, UAG, and TGhr post-OGTT were not significantly different among groups. UAG and TGhr levels did not differ significantly among the normal glucose tolerance (NGT), IFG and NDDM groups, but they decreased obviously in the IFG+IGT and impaired glucose tolerance (IGT) groups. The NDDM group had larger VFA than the NGT, IGT, and IFG+IGT groups, even after adjustment for height, it was still larger than the NGT group. The factors such as dyslipidemia and obesity which are prone to develop insulin resistance (IR) and decrease insulin sensitivity (IS) were negatively correlated with UAG and TGhr, positively with AG/UAG, while no correlations with AG. In terms of evaluating IS and IR, AG/UAG ratio may be superior in AG concentration. Our findings suggest that relative sufficiency of AG, the deficiency of TGhr and UAG are already present in IFG+IGT patients. We speculate that there is UAG resistance in severe hyperglycemia (diabetic state), which could produce elevated TGhr and UAG compared to IFG+IGT group. In the development of T2D, increase of VFA could be the initiating factor, leading elevated AG, reduced UAG, IR, decreased IS, and finally hyperglycemia.

Associations of the PTEN -9C>G polymorphism with insulin sensitivity and central obesity in Chinese.

BACKGROUND: Phosphatase and tensin homolog on chromosome 10 gene (PTEN) is known as a tumor-suppressor gene. Previous studies demonstrated that PTEN dysfunction affects the function of insulin. However, investigations of PTEN single nucleotide polymorphisms (SNPs) and IR-related disease associations are limited. The aim of the present study was to investigate whether its polymorphism could be involved in the risk of metabolic syndrome (MetS). METHODS: The genotype frequency of PTEN -9C>G polymorphism was determined by using a Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) method in 530 subjects with MetS and 202 healthy control subjects of the Han Ethnic Chinese population in a case-control analysis. RESULTS: The PTEN -9C>G polymorphism was not associated with MetS or its hyperglycemia, hypertension and hypertriglyceridemia components. In the control individuals aged <60 years or ≥60 years, the CG genotype individuals had lower insulin sensitivity than CC individuals (P<0.05). In the <60-year-old MetS group and normal glucose tolerance (NGT) subgroup, the CG individuals had lower insulin sensitivity and higher waist circumference (WC) and waist-height-ratio (WHtR) than CC individuals (P<0.05). Multiple linear regression analysis showed that the PTEN polymorphism (P=0.001) contributed independently to 4.2% (adjusted R(2)) of insulin sensitivity variance (estimated by Matsuda ISI), while age (P=0.004), gender (P=0.000) and the PTEN polymorphism (P=0.032) contributed independently to 5.6% (adjusted R(2)) of WHtR variance. CONCLUSIONS: The CG genotype of PTEN -9C>G polymorphism was not associated with MetS and some of its components as well. However, it may not only decrease insulin sensitivity in the healthy control and MetS in pre-elderly or NGT subjects, but may also increase the risk of central obesity among these MetS individuals.