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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.

Free access

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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João P Cunha-Guimaraes, Maria P Guarino, Ana T Timóteo, Iolanda Caires, Joana F Sacramento, Maria J Ribeiro, Mafalda Selas, João C P Santiago, Miguel Mota-Carmo, and Silvia V Conde

Objective

The carotid bodies (CBs) are peripheral chemoreceptor organs classically described as being O2 sensors, which are increasingly emerging as core players in metabolic control. Herein we evaluated CB activity in prediabetes patients and determined its correlation with dysmetabolism clinical features.

Design and methods

Prediabetes patients were recruited at the Cardiology Service, Hospital Santa Marta, Centro Hospitalar Lisboa Central, EPE (CHLC-EPE). The study was approved by CHLC-EPE and NOVA Medical School Ethics Committee. Thirty-three prediabetic and 14 age-matched, non-prediabetic, volunteers had their peripheral chemosensitivity evaluated by the Dejours test. Serum biomarkers of metabolic disease, insulin sensitivity (HOMA-IR), blood pressure, carotid intima-media thickness (cIMT) and glucose tolerance were assessed.

Results

CB chemosensitivity was significantly increased in prediabetic group (P < 0.01). Fasting blood, glucose intolerance, fasting insulin and HOMA-IR were significantly higher in prediabetes patients. Insulin resistance correlated both with peripheral chemosensitivity, assessed by the Dejours test (P < 0.05) and with abdominal circumference (P < 0.01). HbA1c correlated with HOMA-IR (P < 0.05) and left cIMT (P < 0.05) in prediabetes patients.

Conclusions

We conclude that CB is overactive in prediabetes subjects and that peripheral chemosensitivity correlates with fasting insulin and insulin resistance representing a novel non-invasive functional biomarker to forecast early metabolic disease.

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Jingjing Jiang, Xue Liu, Xiaotian Liu, Zhongyan Tian, Haiqing Zhang, Xinling Qian, Zhicheng Luo, Dandan Wei, Shuna Jin, Chongjian Wang, and Zhenxing Mao

Objective

Previous studies have uncovered a progestin-only contraceptive association with an increased risk of diabetes, but limited studies have explored the relationship of endogenous progesterone and pregnenolone levels with diabetes status. A case–control study was conducted in Henan Rural Cohort (register number: ChiCTR-OOC-15006699) to evaluate the dose–response independent and interactive relationship of progesterone and pregnenolone levels with prediabetes and type 2 diabetes mellitus (T2DM) in Chinese rural population.

Design

A case-control study.

Methods

A total of 798 T2DM patients, 779 prediabetes patients, and 782 individuals with normal fasting plasma glucose were included in this study. Serum progesterone and pregnenolone were detected by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent effects of progesterone and pregnenolone on prediabetes and T2DM. Interactive plots were employed to examine the interaction effects of progesterone and pregnenolone.

Results

Progesterone in the fourth versus first quartile was positively associated with prediabetes (odds ratio (OR) (95% CI): 2.66 (1.99–3.55)) and T2DM (OR (95% CI): 6.41 (4.57–8.98)), whereas pregnenolone in the fourth versus first quartile was inversely related to prediabetes (OR (95% CI): 0.23 (0.16–0.33)) and T2DM (OR (95% CI): 0.44 (0.31–0.62)). Additionally, the nonlinear dose–response associations between progesterone and pregnenolone with prediabetes and T2DM were found. Interactive effects of progesterone and pregnenolone on prediabetes and T2DM were observed, and these significant associations remained in gender-stratified analysis.

Conclusions

Prediabetes and T2DM were positively linked to serum concentration of progesterone and negatively related to pregnenolone in a dose–response manner in Chinese rural population.

Free access

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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João Pedro Ferreira, Zohra Lamiral, Constance Xhaard, Kévin Duarte, Emmanuel Bresso, Marie-Dominique Devignes, Edith Le Floch, Claire Dandine Roulland, Jean-François Deleuze, Sandra Wagner, Bruno Guerci, Nicolas Girerd, Faiez Zannad, Jean-Marc Boivin, and Patrick Rossignol

Objective:

Determining the factors associated with new-onset pre-diabetes and type 2 diabetes mellitus (T2D) is important for improving the current prevention strategies and for a better understanding of the disease.

Design:

To study the factors (clinical, circulating protein and genetic) associated with new onset pre-diabetes and T2D in an initially healthy (without diabetes) populational familial cohort with a long follow-up (STANISLAS cohort).

Methods:

A total of 1506 participants attended both the visit 1 and visit 4, separated by ≈20 years. Over 400 proteins, GWAS and genetic associations were studied using models adjusted for potential confounders. Both prospective (V1 to V4) and cross-sectional (V4) analyses were performed.

Results:

People who developed pre-diabetes (n = 555) and/or T2D (n = 73) were older, had higher BMI, blood pressure, glucose, LDL cholesterol, and lower eGFR. After multivariable selection, PAPP-A (pappalysin-1) was the only circulating protein associated with the onset of both pre-diabetes and T2D with associations persisting at visit 4 (i.e. ≈20 years later). FGF-21 (fibroblast growth factor 21) was a strong prognosticator for incident T2D in the longitudinal analysis, but not in the cross-sectional analysis. The heritability of the circulating PAPP-A was estimated at 44%. In GWAS analysis, the SNP rs634737 was associated with PAPP-A both at V1 and V4. External replication also showed lower levels of PAPP-A in patients with T2D.

Conclusions:

The risk of developing pre-diabetes and T2D increases with age and with features of the metabolic syndrome. Circulating PAPP-A, which has an important genetic component, was associated with both the development and presence of pre-diabetes and T2D.

Free access

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.

Free access

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.

Free access

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.

Restricted access

Maria-Elina Mosorin, Annina Haverinen, Meri-Maija Ollila, Tanja Nordström, Jari Jokelainen, Sirkka Keinänen-Kiukaanniemi, Katri Puukka, Aimo Ruokonen, Juha Auvinen, Terhi Piltonen, Laure Morin-Papunen, and Juha S Tapanainen

Objective

The use of combined hormonal contraceptives (CHCs) worsens glucose tolerance, but the risk for glucose metabolism disorders remains controversial.

Design

The study is a prospective longitudinal population-based cohort study.

Methods

The study was based on a cohort population that comprised 1879 women born in 1966. At age 46, the women answered a questionnaire on contraceptive use and underwent an oral glucose tolerance test. Glucose metabolism indices were evaluated in current CHC (n=153), progestin-only contraceptive (POC, n=842), and non-hormonal contraceptive users (n=884).

Results

In the entire study population, current CHC use was significantly associated with prediabetes (OR 2.0, 95% CI 1.3-3.2) and type 2 diabetes (OR 3.3, 95% CI 1.1-9.7) compared to non-hormonal contraceptive use. After five years of use, the prediabetes risk increased 2.2-fold (95% CI 1.3-3.7) and type 2 diabetes risk increased 4.5-fold (95% CI 1.5-13.5). Compared with the current POC use, current CHC use was significantly associated with prediabetes (OR 1.9, 95% CI 1.2-3.0). Current POC use was not associated with any glucose metabolism disorders. The results prevailed after adjusting for body mass index and socioeconomic status.

Conclusions

CHC use in perimenopausal women was associated with a significantly increased risk of glucose metabolism disorders. This association should be considered in women with increased metabolic risk.