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Yun Shen, Peng Wang, Leishen Wang, Shuang Zhang, Huikun Liu, Weiqin Li, Nan Li, Wei Li, Junhong Leng, Jing Wang, Huiguang Tian, Cuilin Zhang, Jaakko Tuomilehto, Xilin Yang, Zhijie Yu and Gang Hu

Aims

To compare risks of early postpartum diabetes and prediabetes in Chinese women with and without gestational diabetes mellitus (GDM) during pregnancy.

Subjects and methods

Tianjin GDM observational study included 1263 women with a history of GDM and 705 women without GDM who participated in the urban GDM universal screening survey by using World Health Organization’s criteria. Postpartum diabetes and prediabetes were identified after a standard oral glucose tolerance test. Cox proportional hazards regression was used to assess risks of postpartum diabetes and prediabetes between women with and without GDM.

Results

During a mean follow-up of 3.53 years postpartum, 90 incident cases of diabetes and 599 incident cases of prediabetes were identified. Multivariable-adjusted hazard ratios among women with prior GDM, compared with those without it, were 76.1 (95% CI: 23.6–246) for diabetes and 25.4 (95% CI: 18.2–35.3) for prediabetes. When the mean follow-up extended to 4.40 years, 121 diabetes and 616 prediabetes cases were identified. Women with prior GDM had a 13.0-fold multivariable-adjusted risk (95% CI: 5.54-30.6) for diabetes and 2.15-fold risk (95% CI: 1.76-2.62) for prediabetes compared with women without GDM. The positive associations between GDM and the risks of postpartum diabetes and prediabetes were significant and persistent when stratified by younger and older than 30 years at delivery and normal weight and overweight participants.

Conclusions

The present study indicated that women with prior GDM had significantly increased risks for postpartum diabetes and prediabetes, with the highest risk at the first 3–4 years after delivery, compared with those without GDM.

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Guoying Wang, Xin Liu, Katherine Kaufer Christoffel, Shanchun Zhang, Binyan Wang, Rong Liu, Zhiping Li, Xue Liu, Wendy J Brickman, Donald Zimmerman, Xiping Xu and Xiaobin Wang

Objective

This study investigated the associations of plasma leptin levels with insulin resistance (IR) and prediabetes in relatively lean, rural Chinese men and women.

Design and methods

This study included 574 subjects aged 21–45 years from a community-based twin cohort. Plasma leptin concentrations were measured by sandwich immunoassays using flowmetric xMAP technology. Prediabetes was defined based on fasting plasma glucose and 75-g oral glucose tolerance test. Multivariate linear and logistic regression analyses were used to investigate gender-specific associations of leptin with IR measures and prediabetes, adjusting for intra-twin correlation, measures of adiposity, and other pertinent covariates.

Results

The body mass index is 22.3±2.7 kg/m2 in men and 22.5±2.7 kg/m2 in women. Leptin levels were positively associated with IR. Individuals with higher tertiles of leptin also had increased risk of prediabetes with odds ratios (OR) of 2.6 (95% confidence interval (CI): 1.4–5.1) and 4.3 (95% CI: 2.1–8.7) in men; OR of 1.1 (95% CI: 0.6–2.1) and 3.1 (95% CI 1.5–6.2) in women for second and third tertile respectively. These associations were attenuated after further adjusting for adiposity measurements only in men. The leptin–prediabetes associations disappeared after adjusting for the homeostatic model assessment of IR in both genders.

Conclusion

In this sample of relatively lean rural Chinese adults, plasma leptin levels were associated with IR and prediabetes in a dose–response fashion, which were not totally explained by adiposity. Our data emphasize that prediabetes is not all about obesity, and leptin may be an additional biomarker for screening individuals at high risk for prediabetes in this population.

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Sin Gon Kim, Ohk Hyun Ryu, Hee Young Kim, Kye Won Lee, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Juneyoung Lee, Sei Hyun Baik and Dong Seop Choi

Objective: Thiazolidinediones have favorable influences on surrogate markers of atherosclerosis such as adiponectin, and arterial stiffness in diabetic patients. However, it is not well known whether these beneficial effects occur in subjects without diabetes, such as prediabetes or the non-diabetic metabolic syndrome (MetS). The present study was therefore designed to evaluate the effectiveness of the insulin-sensitizing agent rosiglitazone on circulating adipocytokine levels and brachial-ankle pulse wave velocity (baPWV) in non-diabetics.

Design and methods: Ninety-nine subjects with prediabetes or non-diabetic MetS were randomly assigned to either rosiglitazone or an untreated control group (50 and 49 subjects respectively). The rosiglitazone group was treated daily for 12 weeks with 4 mg rosiglitazone. All subjects received a 75 g oral glucose test (OGTT) before and after treatment. In addition, baPWV, together with the levels of adiponectin, resistin, and high sensitivity C-reactive protein (hsCRP) were determined.

Results: Rosiglitazone treatment significantly increased circulating adiponectin levels (P < 0.001) relative to the control group (P = 0.21). Plasma resistin levels were unchanged in both the rosiglitazone-treated and -untreated groups, but baPWV and hsCRP were significantly decreased (P < 0.001 and P = 0.003 respectively) in the rosiglitazone group only. Multiple linear regression analysis showed that changes in plasma adiponectin and baPWV were significantly affected by rosiglitazone treatment.

Conclusions: These data suggest that rosiglitazone may have an anti-atherogenic effect in subjects with prediabetes or non-diabetic MetS.

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Jae Kyung Lee, Kyunga Kim, Younjhin Ahn, Mihi Yang and Jung Eun Lee

Background

The association between coffee intake and type 2 diabetes may be modulated by common genetic variation.

Objective

The purpose of this study was to examine the association between habitual coffee intake and the risk of type 2 diabetes and to determine whether this association varied by genetic polymorphisms related to type 2 diabetes in Korean adults.

Design and methods

A population-based cohort study over a follow-up of 4 years was conducted. A total of 4077 Korean men and women aged 40–69 years with a normal glucose level at baseline were included. Coffee intake was assessed using a validated food frequency questionnaire, and incident type 2 diabetes or prediabetes was defined by oral glucose tolerance test or fasting blood glucose test. The genomic DNA samples were genotyped with the Affymetrix Genome-Wide Human SNP Array 5.0, and nine single-nucleotide polymorphisms related to type 2 diabetes in East Asian populations were extracted.

Results

A total of 120 cases of type 2 diabetes and 1128 cases of prediabetes were identified. After adjustment for potential confounding factors, we observed an inverse association, but without any clear linear trend, between coffee intake and the combined risk of type 2 diabetes and prediabetes. We found that inverse associations between habitual coffee intake and the combined risk of type 2 diabetes and prediabetes were limited to those with the T-allele (GT/TT) of rs4402960 in IGF2BP2, those with the G-allele (GG/GC) of rs7754840 in CDKAL1, or those with CC of rs5215 in KCNJ11.

Conclusion

We found a lower risk of prediabetes and type 2 diabetes combined with coffee intake among individuals with the GT/TT of IGF2BP2 rs4402960, GG/GC of CDKAL1 rs7754840, or CC of KCNJ11 rs5215, which are known to be related to type 2 diabetes in East Asians.

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Peter G Noordzij, Eric Boersma, Frodo Schreiner, Miklos D Kertai, Harm H H Feringa, Martin Dunkelgrun, Jeroen J Bax, Jan Klein and Don Poldermans

Objective: To determine the relationship between preoperative glucose levels and perioperative mortality in noncardiac, nonvascular surgery.

Research design and methods: We performed a case–control study in a cohort of 108 593 patients who underwent noncardiac surgery at the Erasmus MC during 1991–2001. Cases were 989 patients who underwent elective noncardiac, nonvascular surgery and died within 30 days during hospital stay. From the remaining patients, 1879 matched controls (age, sex, calendar year, and type of surgery) were selected. Information was obtained regarding the presence of cardiac risk factors, medication, and preoperative laboratory results. Preoperative random glucose levels <5.6 mmol/l (110 mg/dl) were normal. Impaired glucose levels in the range of 5.6–11.1 mmol/l were prediabetes. Glucose levels ≥11.1 mmol/l (200 mg/dl) were diabetes.

Results: Preoperative glucose levels were available in 904 cases and 1247 controls. A cardiovascular complication was the primary cause of death in 207 (23%) cases. Prediabetes glucose levels were associated with a 1.7-fold increased mortality risk compared with normoglycemic levels (adjusted odds ratio (OR) 1.7 and 95% confidence interval (CI) 1.4–2.1; P<0.001). Diabetes glucose levels were associated with a 2.1-fold increased risk (adjusted OR 2.1 and 95% CI 1.3–3.5; P<0.001). In cases with cardiovascular death, prediabetes glucose levels had a threefold increased cardiovascular mortality risk (adjusted OR 3.0 and 95% CI 1.7–5.1) and diabetes glucose levels had a fourfold increased cardiovascular mortality risk (OR 4.0 and 95% CI 1.3–12).

Conclusions: Preoperative hyperglycemia is associated with increased (cardiovascular) mortality in patients undergoing noncardiac, nonvascular surgery.

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Elisabeth Lerchbaum, Verena Schwetz, Albrecht Giuliani and Barbara Obermayer-Pietsch

Objective

There is evidence suggesting a strong genetic background of polycystic ovary syndrome (PCOS). We aim to study the metabolic and endocrine characteristics of PCOS women with and without a family history (FHx) of type 2 diabetes mellitus (T2DM) and PCOS.

Design

Cross-sectional study.

Methods

We analysed the association of T2DM FHx and PCOS FHx with metabolic and endocrine parameters in 714 PCOS women.

Results

A positive FHx of T2DM and PCOS were prevalent in 36.8 and 21.4% of PCOS women respectively. We found an independent association of T2DM FHx with central fat accumulation, obesity, prediabetes, metabolic syndrome (MS), insulin resistance, low HDL and elevated blood pressure (P<0.05 for all). PCOS FHx was independently associated with prediabetes (P<0.05). We observed an independent association of PCOS FHx with clinical and biochemical hyperandrogenism (P<0.05 for all), whereas there was no independent association of T2DM FHx with hyperandrogenism. PCOS women with a positive FHx of both T2DM and PCOS had an adverse metabolic and endocrine profile including a linear increase in risk of obesity, central fat accumulation, MS, prediabetes and low HDL (P<0.05 for all).

Conclusions

Our findings suggest that the assessment of FHx might allow risk stratification of PCOS women, which is important considering the high prevalence of PCOS.

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Carla Giordano, Valentina Guarnotta, Rosario Pivonello, Marco Calogero Amato, Chiara Simeoli, Alessandro Ciresi, Alessia Cozzolino and Annamaria Colao

Objective

Diabetes mellitus (DM) is one of the most frequent complications of Cushing's syndrome (CS). The aim of this study was to define the changes in insulin sensitivity and/or secretion in relation to glucose tolerance categories in newly diagnosed CS patients.

Design

Cross-sectional study on 140 patients with CS.

Methods

A total of 113 women (80 with pituitary disease and 33 with adrenal disease, aged 41.7±15.7 years) and 27 men (19 with pituitary disease and eight with adrenal disease, aged 38.1±20.01 years) at diagnosis were divided according to glucose tolerance into normal glucose tolerance (CS/NGT), impaired fasting glucose and/or impaired glucose tolerance (CS/prediabetes), and diabetes (CS/DM) groups.

Results

Seventy-one patients had CS/NGT (49.3%), 26 (18.5%) had CS/prediabetes and 43 (30.8%) had CS/DM. Significant increasing trends in the prevalence of family history of diabetes (P<0.001), metabolic syndrome (P<0.001), age (P<0.001) and waist circumference (P=0.043) and decreasing trends in HOMA-β (P<0.001) and oral disposition index (DIo) (P<0.002) were observed among the groups. No significant trends in fasting insulin levels, area under the curve for insulin (AUCINS), Matsuda index of insulin sensitivity (ISI-Matsuda) and visceral adiposity index were detected.

Conclusions

Impairment of glucose tolerance is characterized by the inability of β-cells to adequately compensate for insulin resistance through increased insulin secretion. Age, genetic predisposition and lifestyle, in combination with the duration and degree of hypercortisolism, strongly contribute to the impairment of glucose tolerance in patients with a natural history of CS. A careful phenotypic evaluation of glucose tolerance defects in patients with CS proves useful for the identification of those at a high risk of metabolic complications.

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Tove Lekva, Jens Bollerslev, Kristin Godang, Marie Cecilie Paasche Roland, Camilla Margrethe Friis, Nanna Voldner, Tore Henriksen and Thor Ueland

Context

Glucose intolerance in pregnancy predicts an increased risk of future type 2 diabetes.

Objective

The aim of the study was to evaluate glucose metabolism in women with and without gestational diabetes mellitus (GDM) at 5 years follow-up and identify risk factors associated with disturbed glucose metabolism post-partum.

Design

This follow-up study included 300 consecutively enrolled women from a previous population-based cohort study. The participants underwent oral glucose tolerance test under pregnancy and in the follow-up study, in addition to dual-energy X-ray absorptiometry in the follow-up study.

Results

Fifty-two women (17.7%) were found to have GDM in pregnancy with an odds ratio of 4.8 developing prediabetes 5 years later. β-cell function, but not insulin resistance or sensitivity, was reduced in the follow-up study after adjusting for known risk factors. Furthermore, visceral fat content at follow-up was increased in GDM women compared to non-GDM women, and the β-cell function declined with increasing visceral fat in both groups but was more pronounced in the women with previous GDM.

Conclusions

Women with GDM are at increased risk of developing prediabetes and have a decreased β-cell function 5 years post-partum that is associated with increased visceral fat mass.

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Se Eun Park, Nam Seok Lee, Ji Woo Park, Eun-Jung Rhee, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Cheol-Young Park and Byung-Soo Youn

Objective

Serum concentrations of retinol-binding protein 4 (RBP4) are elevated in type 2 diabetes and associated with the severity of insulin resistance; however, there are few data about the relationship between urinary RBP4 levels and metabolic parameters. We assessed urinary RBP4 as a new biomarker by establishing its relationship with clinical parameters associated with insulin resistance and urinary albumin excretion.

Design and methods

We measured RBP4 in the serum and urine of 689 subjects with diverse glucose tolerance status. We also evaluated the relationship between urinary RBP4 and cardiometabolic risk factors, including insulin resistance, high-sensitivity C-reactive protein (hsCRP), arterial stiffness, and microalbuminuria.

Results

Urinary RBP4 levels were higher in insulin-resistant subjects with prediabetes or type 2 diabetes than in subjects with normal glucose tolerance (NGT) (type 2 diabetes>prediabetes>NGT; all P<0.001). Urinary RBP4 correlated strongly with homeostasis model assessments of insulin resistance (HOMA-IR), fasting glucose, triglycerides, blood pressure, hsCRP, arterial stiffness, estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio (all P<0.01). HOMA-IR and arterial stiffness were found to be independent determinants of urinary RBP4 concentration. Furthermore, urinary RBP4 was highly predictive of microalbuminuria (odds ratio 2.6, 95% CI 1.6–4.2), even after adjustment for other metabolic parameters. The area under the ROC curve for urinary RBP4 to detect the presence of microalbuminuria was 0.80±0.02 (95% CI 0.76–0.84) and the cut-off value was 157.01 μg/gCr.

Conclusions

Urinary RBP4 concentrations were elevated in patients with dysregulation of glucose metabolism and were related to various cardiometabolic risk factors including insulin resistance, inflammation, and microalbuminuria.

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Cornelia Huth, Simon Beuerle, Astrid Zierer, Margit Heier, Christian Herder, Thorsten Kaiser, Wolfgang Koenig, Florian Kronenberg, Konrad Oexle, Wolfgang Rathmann, Michael Roden, Sigrid Schwab, Jochen Seissler, Doris Stöckl, Christa Meisinger, Annette Peters and Barbara Thorand

Objective

Iron has been suggested to play a role in the etiology of type 2 diabetes mellitus (T2DM). Except for ferritin, evidence is sparse for other markers of iron metabolism that are regulated differently and might act through independent pathways. We therefore investigated the associations of serum ferritin, transferrin, soluble transferrin receptor (sTfR), transferrin saturation (TSAT), sTfR-to-log10ferritin (sTfR-F) index, and iron with impaired glucose metabolism (IGM/‘prediabetes’), T2DM, and four continuous glucose and insulin traits.

Design and methods

Data from 2893 participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (Germany) was investigated through regression analysis. The results were adjusted for socio-demographic, life-style, and obesity measures as well as metabolic, inflammatory, and other iron biomarkers following a step-wise approach. Non-linearity was tested by adding a non-linear spline component to the model.

Results

Ferritin and transferrin were positively associated with IGM (fourth vs first sex-specific quartile: ferritin odds ratio (OR)=2.08 (95% CI 1.43–3.04) and transferrin OR=1.89 (95% CI 1.32–2.70)), T2DM (ferritin OR=1.98 (95% CI 1.22–3.22) and transferrin OR=2.42 (95% CI 1.54–3.81)), and fasting as well as 2-h glucose. TSAT (OR=0.55 (95% CI 0.34–0.88)) and iron (OR=0.61 (95% CI 0.38–0.97)) were inversely associated with T2DM, sTfR-F-index was inversely associated with IGM (OR=0.67 (95% CI 0.48–0.95)). There was no strong evidence for non-linear relationships.

Conclusions

The observed associations of several markers of iron metabolism with hyperglycemia and insulin resistance suggest that iron stores as well as iron-related metabolic pathways contribute to the pathogenesis of IGM and T2DM. Moreover, TSAT levels are decreased in T2DM patients.