Risk Of Incident Type 2 Diabetes Mellitus Research Articles

Abstract P518: Prospective Study of Skipping Meals to Lose Weight as a Predictor of Incident Type 2 Diabetes and Coronary Heart Disease: The Canadian 1995 Nova Scotia Health Survey

Introduction: Skipping meals is an increasingly common practice to lose weight among North American adults of all bodyweights. However, due to a lack of long-term studies, the long-term effect of skipping meals to lose weight on cardiometabolic health outcomes such as a diagnosis of type 2 diabetes mellitus (T2DM) or incident coronary heart disease (CHD) remains unknown, although previous short-term studies of skipping meals and risk factors for T2DM and CHD have suggested plausible biological pathways for a relationship to exist in either direction, protective or harmful. Hypothesis: We assessed the hypotheses that skipping meals to lose weight was associated with long-term risk of incident T2DM and CHD in the Canadian 1995 Nova Scotia Health Survey (NSHS95), and that these associations were influenced by cardiometabolic risk factors. Methods: Skipping meals to lose weight was assessed via questionnaire in a cohort of 2,898 adults in the NSHS95 and was linked to population-based health care administrative databases to determine incidence of T2DM and/or CHD in the following 23 years. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for T2DM and CHD. Results: During 23 years of follow-up, 430 incident cases of T2DM and 632 incident cases of CHD were diagnosed. Compared to participants who did not skip meals to lose weight, those who did skip meals to lose weight (2.7%) had an 87% higher risk of T2DM (multivariable-adjusted HR=1.87, 95% CI: 1.11-3.17). This association was no longer present after adjustment for baseline body mass index (BMI) (HR=1.42, 0.83-2.42). After stratification by BMI, skipping meals was associated with T2DM among participants who had BMI <25 kg/m 2 (n=1,030; HR=4.42, 1.01-19.30) but not among participants with BMIs of 25-29.9 kg/m 2 (n=1,123; HR=1.07, 0.39-2.96) or 30+ kg/m 2 (n=586; HR=1.21, 0.61-2.39). The multivariable-adjusted (including BMI) association was also present within participants with elevated cholesterol (n=1,450; HR=1.88, 1.00-3.53) and high blood pressure (n=1,363; HR=2.07, 1.11-3.85), but not among those without. No significant association was observed between skipping meals to lose weight and CHD risk before (HR=1.14, 0.67-1.96) or after adjustment for BMI (HR=1.05, 0.61-1.81), or within subgroups. Conclusion: These findings suggest that skipping meals to lose weight may be a predictive modifiable risk factor for developing T2DM over time, especially among people with a BMI <25 kg/m 2 , potentially working in connection or iteration with other T2DM risk factors. With the growing number of popular diets that include skipping meals, future studies are warranted to understand perturbations of potential metabolic consequences.

1514-P: Serum Amylase (AMY) Level and Its Chronological Change as a Predictor of Incident Type 2 Diabetes Mellitus (T2DM)

Low serum AMY is commonly observed in people with a history of pancreatitis, which is a well-known predictor of T2DM. However, few longitudinal studies investigated whether low AMY could be predictive of T2DM, especially considering the effects of baseline HbA1c. Also, it is unclear if a change in AMY is predictive of incident T2DM. Thus, we investigated the impact of AMY and its chronological change on the risk of T2DM considering baseline HbA1c. Analyzed were 5306 individuals who had health examinations yearly for 7 y. We monitored the change in AMY values between baseline 1 (first visit) and baseline 2 (2 y later) and ratio of baseline 2 to baseline 1. During the 5-y follow-up, T2DM occurred in 716 patients. Multivariate Cox analysis showed that both a lower AMY at baseline 2 (HR of Quintile 1, 1.44[1.11-1.88] vs. Q5 as ref.) and a larger AMY decline from baseline 1 (HR of <85%, 1.37[1.01-1.87] vs. ≥115% as a ref.) were independent and significant predictors for incident T2DM. In a stratified analysis of 15 groups divided according to the combination of AMY at baseline 2 and chronological change, those with the lowest AMY at baseline 2 and the largest decline in AMY had a significantly increased risk for incident T2DM (Fig. 1 HR of Quintile 1, < 89.9%, 1.57[1.11, 2.23] vs. Q3/≥100% as ref.). These findings imply the clinical relevance of using the AMY level and its chronological changes to assess risk of incident T2DM. Disclosure D. Ishii: None. K. Fujihara: None. R. Nedachi: None. M. Harada: None. Y. Matsubayashi: None. K. Saito: None. S. Kodama: None. R. Yamamoto-Honda: None. Y. Arase: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.

Serum Immunoglobulin Concentrations and Risk of Type 2 Diabetes Mellitus in Adults: A Prospective Cohort Study

Background: Type 2 diabetes mellitus (T2DM) has emerged as a global epidemic due to lifestyle changes and urbanization. Numerous experimental studies have demonstrated that inflammation plays an important role in the etiology of T2DM. However, very few prospective studies are available on the link between immunoglobulins concentrations and risk of T2DM in adults. Hence, the aim of the present study was to investigate the associations between immunoglobulin levels and the risk of incident T2DM in a large cohort. Methods: The prospective study was performed among 6,245 adults in Tianjin, China. Participants without T2DM history were followed up for 1 to 8 years with a mean follow-up duration of 3*64 years. T2DM were diagnosed in accordance with the guidelines of the American Diabetes Association. Serum immunoglobulins levels were measured by the immunonephelometric assay. T2DM and immunoglobulins levels were assessed yearly during the follow-up. Multiple COX regression models were used to assess the association between serum immunoglobulin concentrations and the incidence of T2DM. Findings: The incidence of T2DM was 16*58 per 1,000 person-years. After multivariate adjustments, compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0*64(0*47-0*89), 1*01(0*75-1*35), 0*64(0*46-0*90) and 1*80(1*34-2*42) (P for trend were <0*01, 0*75, 0*01 and <0*0001), respectively. Interpretation: Our findings firstly suggest that IgG, IgM and IgA concentrations were independent predictors for developing T2DM. However, we found no association between IgE concentrations and the incidence of T2DM. Funding Statement: This study was supported by grants from the National Natural Science Foundation of China (No. 91746205, 81872611, and 81673166), China Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by the Institutional Review Board of Tianjin Medical University. All participants had provided written informed consent prior to participation in the study.

Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort.

SummaryObjectivePrevious studies suggest that androgens have a sexually dimorphic impact on metabolic dysfunction. However, the sex‐specific link between circulating androgens and risk of type 2 diabetes mellitus (T2DM) has not been examined in a large scale, longitudinal cohort, a task we undertook in this study.DesignA retrospective cohort study in a UK primary care database.PatientsWe included men and women with available serum testosterone and sex hormone‐binding globulin (SHBG) results.MeasurementsWe categorized serum concentrations according to clinically relevant cut‐off points and calculated crude and adjusted T2DM Incidence Rate Ratios (IRRs and aIRRs).ResultsSerum testosterone concentrations were available in 70 541 men and 81 889 women; serum SHBG was available in 15 907 men and 42 034 women. In comparison to a reference cohort with serum testosterone ≥20 nmol/L, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7 nmol/L (aIRR 2.71, 95% CI 2.34‐3.14, P < 0.001). In women, the risk of T2DM started to increase significantly when serum testosterone concentrations exceeded 1.5 nmol/L, with the highest risk in women with serum testosterone ≥3.5 nmol/L (aIRR 1.98, 95% CI 1.55‐2.52, P < 0.001). These observations were verified in a continuous rather than categorized analysis. The risk of T2DM increased in men and women with serum SHBG <40 and <50 nmol/L, respectively.Conclusions/InterpretationIn this longitudinal study, we found sexually dimorphic associations between serum testosterone and risk of incident T2DM. Androgen deficiency and excess should be considered important risk factors for diabetes in men and women, respectively.

Use of a Metabolic Syndrome Severity Z Score to Track Risk During Treatment of Prediabetes: An Analysis of the Diabetes Prevention Program.

OBJECTIVEWe assessed whether changes in metabolic syndrome (MetS) severity during the treatment of prediabetes are associated with reduced risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD).RESEARCH DESIGN AND METHODSWe analyzed data from the Diabetes Prevention Program (DPP) for 2,476 adults in 1996–1999 with prediabetes randomized to receive treatment with lifestyle modification, metformin, or placebo for 2–3 years and followed through 2014 for T2DM and CVD outcomes. We calculated effect sizes from baseline in a MetS severity z score (MetS-Z) and the individual MetS components, and assessed relationships between 1-year effect size and incident T2DM and CVD using hazard ratios (HRs) and mediation analysis.RESULTSBaseline MetS-Z and its components were associated with risk of incident T2DM and CVD. During year 1 of intervention, MetS-Z and its components decreased most with lifestyle modification, followed by treatment with metformin and placebo. Risk of T2DM within 1–5 years was most strongly associated with 1-year changes in MetS-Z and waist circumference (both HRs for a 1 SD increase = 1.80), whereas the risk of CVD was associated with a 1-year change in MetS-Z, glucose, and systolic blood pressure. In mediation analyses, the effect of lifestyle modification on T2DM risk was mediated by 1-year changes in MetS-Z, waist circumference, glucose, and triglycerides, whereas the effect of metformin was mediated by MetS-Z and glucose.CONCLUSIONSChanges in these risk indicators of MetS severity during intervention in the DPP reflect altered disease risk and may help in tracking earlier responses to treatment and in motivating patients.

The role of triglyceride glucose index in development of Type 2 diabetes mellitus

AimsTriglyceride-Glucose (TyG) is an emerging surrogate indicator of insulin resistance. We explored the role of TyG in development of Type 2 Diabetes Mellitus (T2DM) and elucidated the mechanism for the relationship. Methods4109 subjects without baseline T2DM participated in a community screening programme in 2013–2016. TyG was calculated as Ln[fasting triglyceride level (mg/dl) × fasting plasma glucose (FPG) (mg/dl)/2]. Outcome was T2DM defined as FPG ≥ 7.0 mmol/l; current treatment with anti-diabetes medication; and/or self-reported diabetes on follow-up screening. We used Cox proportion-hazard model to assess risk of T2DM by TyG quartiles at baseline. Binary mediation analysis was performed to examine extent of mediation by TyG between Body Mass Index (BMI) and T2DM development. ResultsAfter 5734.23 person-years of follow-up, T2DM developed in 117 subjects with an incidence of 20.40/1000 person-years. Risk of T2DM incidence was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG (adjusted HR 1.79(95%CI 0.80–3.99), 2.54 (1.18–5.49) and 4.68(2.19–10.01), Ptrend < 0.001) across TyG quartiles. TyG accounted for 35.1% of association between BMI and T2DM development, having adjusted for potential cofounders (p < 0.001). ConclusionsTyG is potentially useful for predicting T2DM in clinical practice. It is a potential mediator of association between BMI and T2DM development.

Statins use and risk of new-onset diabetes in hypertensive patients: a population-based retrospective cohort study in Yinzhou district, Ningbo city, People's Republic of China.

BackgroundReports have suggested that statin use is associated with an increased incidence of type 2 diabetes mellitus (T2DM). Guidelines suggested that statins should be prescribed in hypertensive patients for primary prevention. However, there were very few studies on the risk of T2DM associated with statin use among patients with hypertension in mainland People’s Republic of China.PurposeTo determine the association between statin use and new-onset diabetes mellitus among patients with hypertension in mainland People’s Republic of China.Patients and methodsWe performed a retrospective cohort study of hypertensive patients using the Yinzhou regional health care database from January 1, 2010, to August 31, 2016. Patients aged 30–90 years old without T2DM were eligible for inclusion. We identified new statin initiators and nonusers by using prescription records of inpatients and outpatients. Multivariate Cox model and propensity score methods were used to adjust potential confounders, including age, sex, body mass index, comorbidities, lifestyle characteristics, and baseline antihypertensive drug use. The risk of incident T2DM among statin initiators compared to nonusers was estimated by the Cox proportional hazards model. Propensity scores for statin use were then developed using logistic regression, statin initiators were matched 1:1 with nonusers according to propensity scores with the nearest neighbor matching method within 0.2 caliper width, and Cox regression was again conducted.ResultsAmong 67,993 patients (21,551 statin initiators; 46,442 nonusers), the unadjusted incidence rate of incident T2DM was higher in statin initiators than nonusers (25.68 versus 14.19 events/1,000 person-years; adjusted hazard ratio: 1.55; 95% confidence interval: 1.44–1.66). After propensity score 1:1 matching (19,818 statin initiators; 19,818 nonusers), baseline characteristics between 2 groups were balanced except that the nonusers group was 0.53 years older on average (P<0.001). Then statin use was still associated with a significant increased risk for T2DM in the matched cohort (adjusted hazard ratio: 1.54; 95% confidence interval: 1.41–1.67). Subgroup analyses also demonstrated similar findings.ConclusionOur study indicated an association between statin use and an increased risk of new-onset diabetes mellitus. It provides better understanding of statin and new-onset diabetes mellitus association among hypertensive patients in real-word setting. As an observational study, our findings were prone to unmeasured confounding and bias.

Dynamic status of metabolically healthy overweight/obesity and metabolically unhealthy and normal weight and the risk of type 2 diabetes mellitus: A cohort study of a rural adult Chinese population

We aimed to determine dynamic status of metabolically healthy overweight or obesity (MHO) and metabolically unhealthy and normal weight (MUNW) and the risk of incident type 2 diabetes mellitus (T2DM). Body mass index and metabolic health were assessed on 11,865 eligible participants ≥18 years from 6-year follow-up cohort study of a rural Chinese population. Participants were classified as metabolically healthy and normal weight (MHNW), MHO, MUNW and metabolically unhealthy overweight or obesity (MUO) at both baseline and follow-up examinations. Hazard ratio (HR) and 95% confidence interval (CI) were used to assess baseline and their changes of BMI-metabolic status and the risk of incident T2DM. Risk of T2DM was increased for all participants with baseline MHO, MUNW, and MUO (adjusted HR 1.94, 95% CI 1.33-2.81; 3.10, 95% CI 2.19-4.39; and 6.63, 95% CI 4.94-8.90, all P<0.001, respectively). However, risk of T2DM was increased for participants with transformation from MHO to MUO (4.52, 95% CI 2.42-8.47, P<0.001) as compared with stable MHNW, but not stable MHO (0.53, 95CI 0.20-1.40, P=0.20). Risk of T2DM did not differ between participants with transformation from MUNW to metabolically healthy and those with stable MHNW (P>0.05), but was increased with stable MUNW (5.78, 95% CI 3.15-10.62, P<0.001). The results were consistent when analyses were restricted to participants without baseline impaired fasting glucose level. Our findings provide understanding for differentiating high-risk individuals for incident T2DM in Chinese population.

Grip strength is not associated with incident type 2 diabetes mellitus in healthy adults: The CoLaus study

We examined the association of grip strength with incident type 2 diabetes mellitus (T2DM) in healthy subjects initially aged 50 to 75years after a follow-up of 5.5years and 10.7years. This was a prospective, population-based study derived from the CoLaus (Cohorte Lausannoise) study including 2318 participants (aged 60.2y; 1354 women) free from T2DM at baseline. Grip strength was assessed using a handheld dynamometer. The effect of grip strength on the incidence of T2DM was analyzed by logistic regression. After a follow-up of 5.5years, 190 (8.2%) T2DM cases were identified. In bivariate analysis, participants who developed T2DM had a higher absolute grip strength (35.3±10.6 versus 33.2±10.7kg, P=0.013). Analysis between grip strength expressed in 5kg increment and incident TD2M showed a negative association when adjusted for age and sex [ORs (95% CI): 0.88 (0.79, 0.98)], or for age, sex and body mass index (BMI) [ORs (95% CI): 0.87 (0.78, 097)]. After a follow-up of 10.7years, 131 supplemental (7.3%) T2DM cases were identified, but there was no association between grip strength and incident T2DM in bivariate and multivariable analysis, potentially due to a lack of statistical power. In non elderly healthy adults, the risk of incident T2DM is overall not associated with grip strength over a maximum follow-up of 10.7years. Future studies are warranted to better assess the association between grip strength and incident T2DM in bigger and even younger cohorts.

Concomitant Use of Atypical Antipsychotics With Other Psychotropic Medication Classes and the Risk of Type 2 Diabetes Mellitus

More than half of youth treated with atypical antipsychotic (AAP) medications are also treated with concomitant antidepressants or stimulants. This study assessed the association between antidepressant or stimulant use concomitant with AAPs and the risk of incident type 2 diabetes mellitus (T2DM). Medicaid Analytic eXtract data were used to conduct a retrospective cohort study of youth (aged 5-20 years) who initiated AAP treatment. In AAP-treated youth, concomitant antidepressant (selective serotonin reuptake inhibitors [SSRI]/serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic/other cyclic antidepressants [TCAs], and other antidepressants) or stimulant use was assessed. The risk of incident T2DM was estimated using discrete time failure models, adjusting for disease risk score estimated using >125 baseline and time-dependent covariates. Among 73,224 AAP initiators, 43.0% had concomitant antidepressant use (76.4% were SSRI/SNRIs) and 43.8% had concomitant stimulant use. The study cohort had an average follow-up of 24.8 months (median= 22.0 months, interquartile range [IQR]= 10.0-38.0 months). In current AAP-treated youth, concomitant SSRI/SNRI (relative risk [RR]= 1.84, 95% CI=1.30-2.59) or TCA use (RR= 2.75, 95% CI= 1.28-5.87) was associated with an increased risk of T2DM. By contrast, concomitant use of other antidepressants or stimulants with AAPs was not associated with an increased risk of T2DM. In concomitant users of AAPs and SSRI/SNRIs, the risk of T2DM increased with the duration of SSRI/SNRI use (RR= 2.35, 95% CI= 1.15-4.83 for≥180 days vs. 1-180 days) as well as with the cumulative SSRI/SNRI dose (RR= 1.99, 95% CI= 1.08-3.67 for >2,700 mg vs. 1-2,700 mg fluoxetine dose equivalents), after adjusting for the duration and cumulative dose of AAP use. By contrast, in concomitant users of AAPs and stimulants, neither duration nor cumulative dose of stimulants was associated with an increased risk of T2DM. In AAP-treated Medicaid-insured youth, concomitant SSRI/SNRI use was associated with a heightened risk of T2DM, which intensified with increasing duration and dose.

Bisphosphonates and glucose homeostasis: a population-based, retrospective cohort study.

Evidence suggests that the human skeleton might be involved in the regulation of glucose homeostasis. The objective of the study was to investigate the effect of exposure to bisphosphonates on the risk of incident type 2 diabetes mellitus (T2DM). This was a population-based, retrospective, open cohort study over the period 1995-2010. The study was conducted from The Health Improvement Network database from the United Kingdom in a primary care setting. A total of 35 998 individuals aged older than 60 years, without diabetes at baseline and with more than 1 year's exposure to bisphosphonates, and 126 459 age-, gender-, body mass index- and general practice-matched unexposed individuals participated in the study. There were no interventions. A new diagnosis of T2DM during the 16-year-long observation period, determined by Read codes and adjusted incidence rate ratio in bisphosphonate-exposed compared with unexposed groups, was the main outcome measure. The risk of incident T2DM was significantly lower in patients exposed to bisphosphonates compared with matched controls [adjusted incidence rate ratio 0.52, 95% confidence interval (CI) 0.48-0.56, P < .0001]. In subgroup analyses, the findings remained consistent in males [0.77 (95% CI 0.66-0.89)], females [0.49 (95% CI 0.45-0.53)], obese [0.54 (95% CI 0.50-0.59)], individuals exposed to steroid treatment [0.47 (95% CI 0.34-0.64)], and over different types of bisphosphonate medication. Analysis of duration of treatment suggested a brief increase in the risk of T2DM (1 to 2.5 y of exposure), followed by a progressive, sustained decrease as the years of exposure accumulated. This observational evidence suggests exposure to bisphosphonates was associated with a significant 50% reduction in the risk of incident T2DM.

Leucocyte telomere length and risk of type 2 diabetes mellitus: new prospective cohort study and literature-based meta-analysis.

BackgroundShort telomeres have been linked to various age-related diseases. We aimed to assess the association of telomere length with incident type 2 diabetes mellitus (T2DM) in prospective cohort studies.MethodsLeucocyte relative telomere length (RTL) was measured using quantitative polymerase chain reaction in 684 participants of the prospective population-based Bruneck Study (1995 baseline), with repeat RTL measurements performed in 2005 (n = 558) and 2010 (n = 479). Hazard ratios for T2DM were calculated across quartiles of baseline RTL using Cox regression models adjusted for age, sex, body-mass index, smoking, socio-economic status, physical activity, alcohol consumption, high-density lipoprotein cholesterol, log high-sensitivity C-reactive protein, and waist-hip ratio. Separate analyses corrected hazard ratios for within-person variability using multivariate regression calibration of repeated measurements. To contextualise findings, we systematically sought PubMed, Web of Science and EMBASE for relevant articles and pooled results using random-effects meta-analysis.ResultsOver 15 years of follow-up, 44 out of 606 participants free of diabetes at baseline developed incident T2DM. The adjusted hazard ratio for T2DM comparing the bottom vs. the top quartile of baseline RTL (i.e. shortest vs. longest) was 2.00 (95% confidence interval: 0.90 to 4.49; P = 0.091), and 2.31 comparing the bottom quartile vs. the remainder (1.21 to 4.41; P = 0.011). The corresponding hazard ratios corrected for within-person RTL variability were 3.22 (1.27 to 8.14; P = 0.014) and 2.86 (1.45 to 5.65; P = 0.003). In a random-effects meta-analysis of three prospective cohort studies involving 6,991 participants and 2,011 incident T2DM events, the pooled relative risk was 1.31 (1.07 to 1.60; P = 0.010; I 2 = 69%).Conclusions/InterpretationLow RTL is independently associated with the risk of incident T2DM. To avoid regression dilution biases in observed associations of RTL with disease risk, future studies should implement methods correcting for within-person variability in RTL. The causal role of short telomeres in T2DM development remains to be determined.

Fatty liver score and 15-year incidence of type 2 diabetes.

Both non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL) are strongly associated with obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Recently, also the vitamin D level has been associated with these and may also be associated with fatty liver (FL). Liver function tests (LFTs) are insensitive markers of FL, but use of scores may help in identifying subjects with FL. We studied how LFTs and the FL score predict the development of T2DM in subjects with AFL versus NAFL and low versus high vitamin D levels. A cohort study based on 4,517 participants, aged 40-79, from the representative Mini-Finland Health Survey was carried out. During a follow-up of 15years, 217 T2DM cases occurred. LFTs were determined from serum samples, and the FL score was formed using BMI, fasting glucose, HDL cholesterol, and GGT concentrations. The risk of T2DM incidence in the highest versus lowest quartile was twofold for the LFTs and ninefold for the FL score. A total of 77% (95% confidence interval: 57-87%) of the T2DM cases could have been prevented if all individuals' FL scores had been at the level of the first quartile. Heavy alcohol consumption and low serum vitamin D concentrations were associated with an increased risk of T2DM among individuals with high FL scores. The FL score is a useful tool for diagnosing FL in epidemiological studies. A high FL score predicts increased risk of T2DM, especially when combined with heavy alcohol consumption or low vitamin D levels.

Prospective Evaluation of B-type Natriuretic Peptide Concentrations and the Risk of Type 2 Diabetes in Women

Animal data suggest that natriuretic peptides play an important role in energy metabolism, but prospective studies evaluating a relationship between these peptides and type 2 diabetes mellitus (T2DM) in humans are few and results are conflicting. We used a prospective case-cohort approach (n = 491 T2DM cases, n = 561 reference subcohort) within the Women's Health Study to evaluate baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and the risk of incident T2DM. We also tested for associations between 4 common variants in the natriuretic peptide A and B genes (NPPA and NPPB) and NT-proBNP concentrations (n = 458) and incident T2DM (n = 1372 cases among 22 607 women). Case subjects had higher median baseline body mass index (29.4 vs 25.0 kg/m(2), P < 0.001) and lower baseline median (interquartile range) NT-proBNP concentrations [46.8 ng/L (26.1-83.2) vs 66.7 ng/L (39.3-124.7), P < 0.001]. In proportional hazards models adjusting for established diabetes risk factors, women in the highest quartile of baseline NT-proBNP concentration (≥ 117.4 ng/L) had a 49% reduction in risk of T2DM [hazard ratio (HR) 0.51, 0.30-0.86, P = 0.01] relative to those in the lowest quartile. Two of the 4 tested variants in NPPA and NPPB (rs632793, rs198389) were associated with increased NT-proBNP concentrations and reduced risk of T2DM. For example, each copy of the minor allele of rs632793 was associated with increased NT-proBNP [β (SE) = 0.201 (0.063), P < 0.01] and decreased T2DM risk (HR 0.91, 0.84-0.989, P = 0.026). NT-proBNP concentrations that are high, but still within the reference interval, associate with reduced risk of incident diabetes in women and support a favorable role for natriuretic peptides in the prevention of T2DM.

Antepartum glucose tolerance test results as predictors of type 2 diabetes mellitus in women with a history of gestational diabetes mellitus: A systematic review

Women with a history of gestational diabetes mellitus (GDM) are at high risk for type 2 diabetes mellitus (T2DM). We reviewed prospective studies of antepartum glucose tolerance test results as risk factors for development of T2DM among women with a history of GDM. We searched 4 electronic databases and hand-searched 13 journals for literature published through January 2007. The search strategy consisted of medical subject headings and text words for GDM, T2DM, and other relevant terms. Articles were excluded for the following reasons: (1) not written in English; (2) no human data; (3) no original data; (4) <90% of sample was diagnosed with GDM without a separate analysis for women with GDM; (5) case report or series; (6) diagnosis of GDM not based on 3-hour 100-g oral glucose tolerance test (OGTT) or 2-hour 75-g OGTT; (7) T2DM not evaluated as outcome; (8) no relative measure of association or incidence reported; or (9) design did not address antepartum OGTT as a predictor of T2DM. Two investigators independently reviewed citations, performed serial data abstraction on full articles, and assessed the quality of each article. Data were abstracted for study participants and characteristics, T2DM diagnosis, length of follow-up, regression model covariates, and measures of association and variability. Of 11,400 unique citations, we identified 11 articles that evaluated antepartum glucose testing and risk of T2DM in women with a history of GDM. Five studies found that the fasting blood glucose (FBG) on the antepartum diagnostic OGTT was a significant predictor of T2DM (odds ratio [OR] range: 11.1-21.0; relative risk [RR] range: 1.37-1.5; relative hazard [RH] = 2.47). Risk of incident T2DM was predicted by the antepartum 2-hour OGTT plasma glucose in 3 studies (OR range: 1.02-1.03; RR = 1.3) and by the antepartum OGTT glucose AUC in 3 other studies (OR range: 3.64-15; RH = 2.13). Overall, study quality was limited by high losses to follow-up (>20% in 6 studies) and short duration. Few studies adjusted for adiposity, an established diabetes risk factor. FBG, OGTT 2-hour blood glucose, and OGTT glucose AUC appeared to be strong and consistent predictors of subsequent T2DM among women who met diagnostic criteria for GDM using the OGTT.