Declining ��-Cell Compensation for Insulin Resistance in Hispanic Women With Recent Gestational Diabetes Mellitus: Association with changes in weight, adiponectin, and C-reactive protein

OBJECTIVE

To identify factors associated with declining β-cell compensation for insulin resistance.

RESEARCH DESIGN AND METHODS

In a cohort of Hispanic women with recent gestational diabetes mellitus, oral glucose tolerance tests (OGTTs), intravenous glucose tolerance tests (IVGTTs), and bioelectrical impedance measurements were performed at 15-month intervals for up to 5 years, or until fasting plasma glucose exceeded 140 mg/dl (7.8 mmol/l). Data were analyzed to identify predictors of declining β-cell compensation for insulin resistance (the disposition index [DI]) and to examine the mechanism of weight gain and changes in circulating levels of selected adipokines and inflammatory markers on β-cell compensation decline.

RESULTS

A total of 60 nondiabetic women had a median of four sets of OGTT + IVGTT during a median follow-up of 52 months. Fourteen of the women developed diabetes. None of the baseline characteristics were significantly predictive of a decline in DI. There were significant univariate associations between declining DI and weight gain (specifically fat gain), declining adiponectin and rising C-reactive protein. Multivariate analysis showed that the weight gain was the most significant factor associated with declining DI. The amount of association between weight gain and declining DI was explained 31% by changes in adiponectin and C-reactive protein and 40% by changes in insulin resistance.

CONCLUSIONS

These results identify weight gain as the strongest factor associated with declining β-cell compensation for insulin resistance in Hispanic women at high risk for type 2 diabetes. Such effect may be mediated through at least two effects: alterations in adipokine levels and increasing insulin resistance.Type 2 diabetes is characterized by inadequate pancreatic β-cell compensation for chronic insulin resistance. Longitudinal studies in Pima Indians (1), Caucasian and African Americans (2,3), and Hispanic Americans (2,4) indicate that β-cell function declines on a background of chronic and often worsening insulin resistance as people progress from normal to impaired glucose tolerance and then to diabetes. Much is known about baseline factors that predict a relatively short time to diabetes—factors such as relatively high glucose levels, insulin resistance, and poor β-cell compensation for insulin resistance. Those factors could be important driving forces for the development of diabetes. They could also simply be markers of individuals closest to diabetes at the initiation of follow-up.Much less is known about the cause(s) of the progressive deterioration in β-cell function that leads to impaired glucose tolerance and diabetes. Declining β-cell function has been shown to be associated with weight gain in Pima Indians (5) and with increased fat in women with a family history of type 2 diabetes (6). Glucose and lipid toxicity have been suggested as causes of declining β-cell function (7), although data are lacking from humans to support such an effect over the years that it takes to develop diabetes.We conducted a longitudinal study investigating the pathogenesis of diabetes development in relatively young Hispanic women with recent gestational diabetes mellitus. We observed a progressive decline in β-cell compensation for insulin resistance that was attended by slowly rising glucose levels until β-cell compensation reached very low levels, at which time glucose levels rose to the diabetic range (4). The present analysis examines what baseline characteristics predict the decline in β-cell compensation for insulin resistance and the potential role and mechanism of weight gain and changes in circulating levels of adipokines and inflammatory markers during follow-up on declining β-cell compensation in this high-risk group.     

Effect of Jianpi-yangwei decoction on gut fungi in the patients with gastric cancer undergoing chemotherapy

Background:Our previous study shows that the empirical formula of Chinese medicine Jianpi-yangwei decoction(JYD)can improve the quality of life in patients with gastric cancer undergoing chemotherapy by increasing beneficial gut bacteria and decreasing harmful bacteria.The present study aims to investigate the effect of JYD on gut fungi in patients with gastric cancer undergoing chemotherapy.Methods:A total of 73 patients with gastric cancer undergoing chemotherapy were recruited.Twenty-nine patients in the chemotherapy group were given standard chemotherapy and 44 patients in the observation group were given JYD plus standard chemotherapy.A control group(55 cases)was recruited from the healthy medical examiners.After 3 months of treatment,life-quality score was evaluated and fecal microbiota was tested by high-throughput sequencing based on the 18S rRNA gene.Results:After treatment,life-quality score in the observation group was significantly lower than that in the chemotherapy group(P<0.05).There was no significant difference between the observation and control groups’diversity and richness indices of intestinal fungi.The Chao index for intestinal fungi in the chemotherapy group was significantly lower than that in the observation group(P<0.05).There was a significant difference between the control and chemotherapy groups in the intestinal fungi according to Shannon and Simpson indices(P<0.05).Linear discriminant analysis effect size analysis showed no significant differences among the three groups,but significant difference in intestinal fungi was observed between the observation group and the chemotherapy group.At the genus level,the relative abundance of the Aspergillus genus in the observation and control groups was significantly lower(P<0.05),the relative abundance of the Cutaneotrichosporon,Galactomyces,and Ganoderma genus taxa was significantly higher compared with those in the chemotherapy group(P<0.05),and there was no significant difference between the observation group and control group.Conclusion:JYD can ameliorate chemotherapy-induced fungal dysbacteriosis in patients with gastric cancer undergoing chemotherapy and improve the quality of life of patients.     

Changes in motor function in the unaffected hand ol stroke patients should not be ignored

Motor function changes in the unaffected hand of stroke patients with hemiplegia. These changes are often ignored by clinicians owing to the extent of motor disability of the affected hand. Finger tapping frequency and Lind-mark hand function score showed that the motor function of unaffected hands in stroke patients was poorer than that of a healthy control hand. After 2 weeks of rehabilitation treatment, motor function of the unaffected hand of stroke patients was obviously improved. Therefore, attention should also be paid to motor function in the unaffected hand of stroke patients with hemiplegia during rehabilitation.     

Genes in the serotonin pathway are associated with bipolar affective disorder in a Han Chinese population

Serotonin plays an important role in mood regulation, but the involvement of serotonin pathway genes in the development of bipolar I disorder (BP-I), a mood disorder, is not clear. We selected 21 singlenucleotide polymorphisms (SNPs) within the HTR2A gene, 8 within the SLC6A4 gene and 23 within the TPH2 gene for genotyping using the GoldenGate genotyping assay. A total of 375 patients with BP-I and 475 normal controls were recruited. Two out of 21 SNPs (rs1475196 and rs9567747) in the HTR2A gene and 1/23 SNPs (rs17110566) in the TPH2 gene were significantly associated with BP-I, both genotype-wise and allele-wise. Furthermore, a specific haplotype in the HTR2A gene showed a significant association with BP-I. Our results indicate that the HTR2A and TPH2 genes in the serotonin pathway play important roles in susceptibility to BP-I.