Background Identifying risk factors for postpartum type 2 diabetes in women with gestational diabetes mellitus (GDM) is crucial for effective interventions. We examined whether changes in insulin sensitivity after delivery affects the risk of type 2 diabetes in women with GDM.
Methods This prospective cohort study included 347 women with GDM or gestational impaired glucose tolerance, who attended the follow-up visits at 2 months postpartum and annually thereafter. Changes in insulin sensitivity were calculated using the Matsuda index at GDM diagnosis and at 2 months postpartum (ΔMatsuda index). After excluding women with pregestational diabetes or those followed up only once, we analyzed the risk of postpartum type 2 diabetes based on the ΔMatsuda index tertiles.
Results The incidence of type 2 diabetes at the two-month postpartum visit decreased with increasing ΔMatsuda index tertiles (16.4%, 9.5%, and 1.8%, P=0.001). During a 4.1-year follow-up, 26 out of 230 women who attended more than two follow-up visits (11.3%) developed type 2 diabetes. Compared to the lowest tertile, subjects in the highest ΔMatsuda index tertile showed a significantly reduced risk of type 2 diabetes (hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.93; P=0.036) after adjusting for confounders.
Conclusion Improvement in insulin sensitivity after delivery is associated with a reduced risk of postpartum type 2 diabetes in women with GDM. Postpartum changes in insulin sensitivity could be a useful prediction for future type 2 diabetes development in women with GDM.
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Evaluation of Maternal Factors Affecting Postpartum Insulin Resistance Markers in Mothers with Gestational Diabetes—A Case–Control Study Karolina Karcz, Paulina Gaweł, Barbara Królak-Olejnik Nutrients.2024; 16(22): 3871. CrossRef
It is well known that obesity central obesity is associated with insulin resistance and some studies reported that sex hormones were associated with insulin resistance. Recently, low levels of sex-hormone binding globulin(SHBG), an indirect index of androgenicity, have been observed to predict the development of non-insulin dependent diabetes mellitus(NIDDM) in women and SHBG has been proposed as a marker for insulin resistance. In contrast to findings in women, decreased SHBG did not predict the occurrence of NIDDM in men, so it is suggested that sex hormones may have a different role for insulin resistance between men and women. To investigate the difference of the associations among the body fat distribution, sex hormone and insulin sensitivity index in men and women, we measured body-mass index(BMI) and waist to hip circumference ratio(WHR) and concentrations serum SHBG, total testosterone, free testosterone, and dehydroepiandrosterone sulfate(DHEA-S) concentrations in 29 healthy adults(men:19, women:10) who showed normal glucose tolerance. Insulin sensitivity index(M/I) was measured by euglycemic hyperinsulinemic clamp. There were no differences in age, BMI, fasting plasma glucose, insulin and free fatty acid levels between men and women. WHR of men is higher than that of women(0.82+-0.01 vs. 0.73+-0.01, p=0.002). Insulin sensitivity index(M/I) is similar in men and women(7.80+-0.71 mg/kg/min/uU/ml X 100 vs. 9.74+-0.89 mg/kg/min/uU/ml X 100, p=0.196).In Pearson's correlation, M/I was significantly correlated with BMI(r=-0.69, p<0.01) and WHR(r=-0.68, p<0.01) in men and DHEA-S(r=-0.68, p<0.05) and SHBG(r=0.61, p=0.056) concentrations in women.In multiple regression analysis, M/I had the most significant association with BMI(R^2=0.484, beta=-0.696, p<0.001) in men and DHEA-S(R^2=0.471, beta=-0.686, p<0.05) concentration in women.Conclusively, we found that sex hormones were significantly associated with insulin resistance and the effects of sex hormones on insulin resistance may be different in men and women.
The impairement of glucose metabolism is frequently associated in hyperthyroidism. The present study was performed to determine the effect of the thyroid hormone excess on insulin sensitivity and on insulin secretory function in vivo. Ten newly diagnosed hyperthyroid patients and fifteen healthy control subjects were subjected to frequently sampled intravenous glucose tolerance tests(FSIGT) after an overnight fast. Insulin sensitivity, represented by the insulin sensitivity index(S_1), was assessed by minimal model analysis of FSIGT data. Insulin secretion was measured by the total area under the insulin curve after glucose load.The results were as follows.1) The K_G values, which represent glucose tolerance, were not different between the hyperthyroid patients and the normals(2.2+-0.3 vs. 2.5+-0.3%/min, p>0.05).2) S_1 was significantly decreased in the hyperthyroid patients in comparison to the normals(7.5+-1.4 vs. 2.6+-0.3X10^-4 min^-1/uU/ml, p<0.05).3) The basal insulin concentration was higher in the hyperthyroid patients than in the normals(8.3+-2.4 vs. 4.6+-0.4 uU/ml, p=0.07). In addition, the insulin secretory response to a glucose load was increased in the hyperthyroid patients as evidenced by the peak plasma insulin level(168.2+-30.4 vs. 89.2+-13.9 uU/ml, p<0.05) and by the total area under the insulin curve(2641.1+-443.2 vs. 1696.7+-204.3 min uU/ml, p<0.05).These results clearly demonstrated that insulin sensitivity was impaired in these newly diagnosed hyperthyroid patients. However, glucose tolerance was maintained by the increased insulin secretion.
BACKGROUND Polycystic ovary syndrome (PCOS) is known to be associated with obesity and insulin resistance. The exact mechanism of insulin resistance in PCOS is not completely understood, but there are several pieces of evidence suggesting humoral mediator involvement. Adiponectin, an adipocyte-secreted protein, could be a possible link between adiposity and insulin resistance. This study was performed to see whether the serum adiponectin levels are suppressed in woman with PCOS and if this is associated with the characteristic hormonal and metabolic features of PCOS. METHODS: 20 women with PCOS and 8 normal controls with regular cycles were recruited. The serum adiponectin levels were measured by RIA, and the fasting glucose to insulin ratio (GIR) used as an insulin sensitivity index. RESULTS: The patients with PCOS were classified as lean (BMI < 23 kg/m2, n=9) and obese groups (BMI 25 kg/m2, n=11) based on the WPRO criteria. The GIR was significantly lower in the obese compared to the control group. The adiponectin level was lower in women with PCOS than the controls, but without statistical significance. In 5 of the 20 patients, the GIR was higher than 0.30, which was the lowest limit in the controls, and the adiponectin level was significantly higher than in those patients with a lower GIR. The adiponectin level was significantly correlated with the BMI, subcutaneous and visceral fat areas, post challenge 2 hr glucose, fasting insulin, GIR and SHBG. After adjustment for BMI, adiponectin was significantly correlated with the GIR in all subjects, including the controls. CONCLUSION: The serum adiponectin level was associated with and related to adiposity in women with PCOS; however, adiponectin might be associated with insulin resistance independently from adiposity
In Kyung Jeong, Sung Hoon Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Hyung Joon Yoo, Kyu Jeong Ahn, Jung Hynun Noh, Dong Jun Kim, Kwang Won Kim
J Korean Endocr Soc. 2003;18(4):392-403. Published online August 1, 2003
BACKGROUND Glucocorticoid plays an important role in the control of carbohydrate metabolism. Patients with Cushing's syndrome have been reported to have an increased incidence of carbohydrate intolerance due to peripheral insulin resistance and hyperinsulinemia, although the exact incidence and nature of this disorder have remained unclear. Few results have been published about insulin resistance and insulin secretion according to the level of glucose concentration, or about the reversibility of such defects in patients with Cushing's syndrome. METHODS: To assess the effect of glucocorticoid on the insulin sensitivity and insulin secretion in Cushing's syndrome, 15 patients with Cushing's syndrome were classified into 3 groups (normal glucose tolerance: NGT, impaired glucose tolerance: IGT, diabetes: DM) according to the degree of glucose tolerance based on the oral glucose tolerance test (OGTT). Insulin modified, frequentlysampled, intravenous glucose tolerance test (FSIGT) was performed before and after curative surgery on these patients and on 15 healthy control subjects. Data were evaluated by non-parametric statistical analysis. RESULTS: 1) Among the 15 patients with Cushing's syndrome, 3 (20%) were NGT, 4 (27%) IGT, and 8 (53%) DM, based on OGTT. Twenty-four hour urinary free cortisol (UFC) was significantly higher in the DM group. 2) Insulin sensitivity index (SI) of Cushing's syndrome was significantly lower than that of the control group (P=0.0024), but was not significantly different among the three Cushing's syndrome groups of NGT, IGT and DM. 3) Glucose mediated glucose disposal (SG) (Ed- confirm this abbreviation; it does not seem to match the definition) of Cushing's syndrome was not significantly different from that of the control group. 4) Insulin secretion (AIRg) of Cushing's syndrome tended to be high, but it was not significantly different from that of control. However, according to the level of glucose concentration there was significant difference in AlRg among the three Cushing's syndrome groups (P=0.0031); AIRg of DM was significantly lower than that of NGT. 5) After surgical treatment, parameters of insulin sensitivity and insulin secretion were normalized in 6 cured patients; 1 with NGT, 1 with IGT, and 4 with DM, preoperatively. Median SI of all 6 patients was significantly improved up to the normal range postoperatively (P=0.0022). Median AIRg of these 6 patients was balanced around that of normal control postoperatively (P=0.0286). CONCLUSION: Eighty percent of patients with Cushing's syndrome had abnormality of carbohydrate metabolism. Insulin sensitivity was significantly decreased in Cushing's syndrome. Insulin secretion was significantly higher only in the NGT and IGT groups of Cushing's syndrome. As the hypercortisolemia is exacerbated, insulin secretion is significantly decreased and causes DM, suggesting that glucocorticoid has a direct or indirect toxic effect on the pancreatic beta cell.
BACKGROUND Thyroperoxidase (TPO), a transmembrane heme containing glycoprotein, catalyzes iodide organification and thyroid hormone synthesis. It is a single peptide making a loop with more than one disulfide bond. The tertiary conformational structure is essential for its enzymatic activity and immunogenicity. The proximal histidine is thought to play a major role in enzymatic activity since it is linked to the iron center of the heme. The crystal structure of TPO has not yet been reported, but some have suggested histidine 407 be a putative proximal histidine based on comparison of a.a. sequence for TPO and that for myeloperoxidase. METHODS: The putative histidine 407 and nearby histidine 414 were mutated to arginine to verify their role as the proximal histidine. Using site directed mutagenesis of wild type, human TPO cDNA, mutants H407R and H414R were made. Mutant cDNAs were transiently transfected into COS-7 cells, and the TPO enzyme activities were measured by guaiacol assay. Four cysteine residues around the putative proximal histidines were mutated to serine and their enzymatic activities were measured to check if they were involved in the formation of intra-molecular disulfide bonds. RESULTS: TPO protein expression of H407R- and H414R- transfected cells was confirmed by Western blot, using Hashimoto's IgG as primary antibody. Both the mutants H407R and H414R showed significant peroxidase enzymatic activity, although lower than those of the wild type. None of the cysteine mutants, C375S, C389S, C598S, and C655S, were detected by Hashimoto's IgG ordisplayed any enzymatic activity. CONCLUSION: These data suggest that neither histidine 407 nor histidine 414 functions as the "proximal histidine" in human TPO. All the cysteine residues checked (375, 389, 598, 655) might be involved in the formation of disulfide bonds in TPO molecules, but this hypothesis could not be confirmed. A further search for the other putative histidine residues using the same strategy is needed to define the structure-function relationship in the human TPO molecule.
Ki Hyun Baek, Hyun Jung Tae, Ki Won Oh, Won Young Lee, Chung Kee Cho, Soon Yong Kwon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Choon Choo Kim
J Korean Endocr Soc. 2003;18(3):296-305. Published online June 1, 2003
BACKGROUND Osteoblasts originate from osteoprogenitor cells in bone marrow stroma, termed mesenchymal stem cells (MSCs) or bone marrow stromal cells. Each MSC forms colonies (colony forming units-fibroblasts [CFU-Fs]) when cultured ex vivo. There are some reports about the age-related changes of the number and osteogenic potential of osteoprogenitor cells, but any relationship has not been clearly established in humans. In this study, we counted MSCs using CFU-Fs count and examined the proliferative capacity and differentiation potential of osteoprogenitor cells. Finally, we analyzed how these parameters varied with donor age. METHODS: Bone marrow was obtained from the iliac crest of young (n=6, 27.2+/-8.6 years old) and old (n=10, 57.4+/-6.7 years old) healthy donors. Mononuclear cells, including MSCs, were isolated and cultured in osteogenic medium. In primary culture, we compared the colony-forming efficiency of MSCs between the two groups and determined the matrix calcification. When primary culture showed near confluence, the cells were subcultured. Alkaline phosphatase activity, osteocalcinexpression by RT-PCR and proliferative potential by MTT assay were examined by the time course of secondary culture. RESULTS: At the 15th day of primary culture, the mean number of CFU-Fs was significantly higher in the younger donors (young: 148.3+/-28.9, old: 54.3+/-9.1, p=0.02) and the mean size of CFU-Fs was also larger in the younger donors than the older donors. However, matrix calcification was not different between the two groups (young: 103.6+/-50.6, old: 114.0+/-56.5, p=NS). In secondary culture, alkaline phosphatase activities were significantly lower in the older donors. The younger donors showed peak alkaline phosphatase activity at day 10, while the older donors didn't showed a remarkable peak (young: 935.5+/-115.0U/mg, old: 578.4+/-115.7U/mg, p<0.05). Total cell number as a proliferative index increased progressively during the secondary culture and a significantly greater cell number was noted in the younger donors. Osteocalcin expression was generally upregulated in the younger donors, but this was not statistically significant. CONCLUSION: Our study shows that the number of osteoprogenitor cells is decreased during aging and that the proliferative capacity and differentiation potential of osteoprogenitor cells seem to be reduced during aging.
BACKGROUND Obesity is an important metabolic abnormality as a pathogenesis of non-insulin dependent diabetes mellitus(NIDDM), and genetic factors have been suggested to be involved in the development of obesity and NIDDM. beta 3-adrenergic receptor gene polymorphism has been reported to be related to an earlier onset of NIDDM and increased capacity of weight gain in obesity. The purpose of this study was to investigate the relation of beta 3-adrenergic receptor gene polymorphism to body fat distribution pattern and insulin resistance in female nondiabetic offpsring of patients with NIDDM. METHODS: We assessed the patterns of body fat distribution by anthropometric measurement, bioelectric impedence analysis and computed tomogram; insulin sensitivity by using frequently sampled intravenous glucose tolerance test and the minimal model analysis. We inverstigated the beta 3 -adrenergic receptor gene polymorphism by PCR and RFLP. RESULTS: 1) The frequency of beta 3 adrenergic receptor gene polymorphism was as follows; wild type (Trp64Trp) 69.8%, Trp64Arg heterozygote 26.4%, Arg64Arg homozygote 3.8% in the offspring of patients with NIDDM. According to obesity, there was no significant difference of distribution of Arg64 allele between nonbese and obese subjects. 2) In the mutant subjects with Arg64 allele, the concentrations of total and LDL cholesterol were significantly increased (p<0.01), but fasting serum glucose and insulin, percent body fat, visceral fat area and visceral to subcutaneous fat area ratio were insignificantly increased, SI were insiginificantly decreased. 3) Multiple regression analysis showed that Arg64 allele did not significantly associated with visceral obesity and insulin resistance. CONCLUSION: The beta 3-adrenergic receptor gene polymorphism was related to dyslipidemia, but not related to visceral adiposity or insulin resistance in nondiabetic offspring women of patients with NIDDM. Further prospective studies in these subjects will be needed for the clarification of pathogenetic role of beta 3-adrenergic receptor gene polymorphism in the development of insulin resistance and NIDDM.