Prepregnancy SHBG Concentrations and Risk for Subsequently Developing Gestational Diabetes Mellitus

OBJECTIVE

Lower levels of sex hormone–binding globulin (SHBG) have been associated with increased risk of diabetes among postmenopausal women; however, it is unclear whether they are associated with glucose intolerance in younger women. We examined whether SHBG concentrations, measured before pregnancy, are associated with risk of gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS

This was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up examination (1984–1996) and had a subsequent pregnancy (1984–2009). Eligible women were free of recognized diabetes. Case patients were 256 women in whom GDM developed. Two control subjects were selected for each case patient and were matched for year of blood draw, age at examination, age at pregnancy, and number of intervening pregnancies.

RESULTS

Compared with the highest quartile of SHBG concentrations, the odds of GDM increased with decreasing quartile (odds ratio 1.06 [95% CI 0.44–2.52]; 2.33 [1.07–5.09]; 4.06 [1.90–8.65]; P for trend < 0.001), after adjusting for family history of diabetes, prepregnancy BMI, race/ethnicity, alcohol use, prepregnancy weight changes, and homeostasis model assessment of insulin resistance. Having SHBG levels below the median (<64.5 nmol/L) and a BMI ≥25.0 kg/m² was associated with fivefold increased odds of GDM compared with normal-weight women with SHBG levels at or above the median (5.34 [3.00–9.49]).

CONCLUSIONS

Low prepregnancy SHBG concentrations were associated with increased risk of GDM and might be useful in identifying women at risk for GDM for early prevention strategies.     

Low Prepregnancy Adiponectin Concentrations Are Associated With a Marked Increase in Risk for Development of Gestational Diabetes Mellitus

OBJECTIVE

To examine whether circulating total and high–molecular weight (HMW) adiponectin concentrations, measured before pregnancy, are associated with subsequent risk of gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS

This was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up exam (1984–1996) with a serum sample obtained and who had a subsequent pregnancy (1984–2009). Eligible women were free of recognized diabetes. Case subjects were the 256 women who developed GDM. Two control subjects were selected for each case and matched for year of blood draw, age at exam, age at pregnancy, and number of intervening pregnancies.

RESULTS

Compared with the highest quartile of adiponectin, the risk of GDM increased with decreasing quartile (odds ratio [OR] 1.5 [95% CI 0.7–2.9], 3.7 [1.9–7.2], and 5.2 [2.6–10.1]; P_trend <0.001) after adjustment for family history of diabetes, BMI, parity, race/ethnicity, cigarette smoking, and glucose and insulin concentrations. Similar estimates were observed for HMW (P_trend <0.001). The combined effects of having total adiponectin levels below the median (<10.29 mg/mL) and being overweight or obese (BMI ≥25.0 kg/m²) were associated with a sevenfold increased risk of GDM compared with normal-weight women with adiponectin levels above the median (OR 6.7 [95% CI 3.6–12.5]).

CONCLUSIONS

Prepregnancy low adiponectin concentrations, a marker of decreased insulin sensitivity and altered adipocyte endocrine function, is associated with reduced glucose tolerance during pregnancy and may identify women at high risk for GDM to target for early intervention.Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first diagnosis during pregnancy, is a common complication of pregnancy. Women with a history of GDM have a sevenfold increased risk of developing type 2 diabetes after delivery (1), and the children of women with GDM are more likely to be obese and develop diabetes (2,3). The underlying etiology of GDM appears to be similar to the physiological abnormalities that characterize diabetes outside of pregnancy and is thought to be due to an inability of the pancreatic β-cells to compensate for the increased insulin resistance induced by pregnancy (4,5). The extent to which insulin resistance or reduced insulin sensitivity leading to GDM occurs even years before pregnancy has not been determined in population-based studies. There is increasing interest in identifying prepregnancy risk factors and biomarkers for GDM to inform future preconception prevention strategies, given the proven success of specific prevention strategies for type 2 diabetes in high-risk populations (6).Adiponectin is an abundant adipocyte-derived hormone demonstrated to have actions consistent with protection against insulin resistance, inflammation, and atherosclerosis (7). Total adiponectin circulates in the bloodstream as three discrete complexes: a lower–molecular weight trimer, a mid–molecular weight hexamer, and a high–molecular weight (HMW) complex (8). Some evidence suggests that HMW adiponectin is the isoform that mediates the insulin-sensitizing and antiatherogenic effects (9,10). Prospective studies examining adiponectin and incident type 2 diabetes reported that lower circulating total adiponectin concentrations were associated with a higher risk of type 2 diabetes in a dose-response relationship (11). Both total adiponectin (12) and HMW adiponectin (13) are known to decrease significantly in normal pregnancies in response to decreased insulin sensitivity; therefore, it is important to determine whether prepregnancy levels of adiponectin are related to subsequent risk of GDM in order to clarify the temporal sequence of the association. The aim of this study is to examine the association between prepregnancy total and HMW adiponectin concentrations and the risk of developing GDM and to determine whether these associations are independent of known metabolic risk factors for GDM.     

Gestational Diabetes Mellitus Alone in the Absence of Subsequent Diabetes Is Associated With Microalbuminuria: Results from the Kidney Early Evaluation Program (KEEP)

OBJECTIVE

Women with gestational diabetes mellitus (GDM) maintain a higher risk for recurrent GDM and overt diabetes. Overt diabetes is a risk factor for development of chronic kidney disease (CKD), but GDM alone, without subsequent development of overt diabetes, may also pose a risk for CKD.

RESEARCH DESIGN AND METHODS

This cross-sectional analysis included Kidney Early Evaluation Program (KEEP) participants from 2000 to 2009. Patient characteristics and kidney function among three categories (GDM alone, overt diabetes, and no history of diabetes) were compared. The prevalence of microalbuminuria, macroalbuminuria, and CKD stages 1–2 and 3–5 was assessed using logistic regression.

RESULTS

Of 37,716 KEEP female participants, 571 (1.5%) had GDM alone and 12,100 (32.1%) had overt diabetes. Women with GDM had a higher rate of microalbuminuria but not macroalbuminuria than their nondiabetic peers (10.0 vs. 7.7%) that was substantially lower than the 13.6% prevalence in diabetic women. In multivariate analysis, women with GDM alone, compared with nondiabetic women, demonstrated increased odds of CKD stages 1–2 (multivariate odds ratio 1.54 [95% CI 1.16–2.05]) similar to the odds for women with overt diabetes (1.68 [1.55–1.82]). In stratified analyses, age, race, BMI, and hypertension modified the odds for CKD stages 1 –2 but not CKD stages 3–5 among women with GDM.

CONCLUSIONS

Women with GDM alone have a higher prevalence of microalbuminuria than women without any history of diabetes, translating to higher rates of CKD stages 1–2. These results suggest that GDM, even in the absence of subsequent overt diabetes, may increase the risk for future cardiovascular and kidney disease.Most women who develop diabetes during a pregnancy, gestational diabetes mellitus (GDM), are normoglycemic after delivery but still maintain a higher risk for recurrent GDM, impaired glucose tolerance, and overt diabetes. Indeed, the odds of developing subsequent type 2 diabetes for women with GDM is roughly 5 times higher than that for women with normoglycemic pregnancies in the first 5 years after delivery; the odds rise to more than 9 times higher in the years afterward (1).Although overt diabetes is recognized as a potent risk factor for development of chronic kidney disease (CKD), it is currently unclear whether GDM alone, without subsequent development of overt diabetes, also poses any risk to kidney function. Because certain clinical factors (e.g., waist circumference, BMI, and years postdelivery) have been shown to increase the risk for development of overt diabetes in women with GDM (2), these factors could potentially also modify the risk for development of CKD.We hypothesized that GDM alone would impart an increased risk for CKD and, specifically, that women with GDM would have a level of risk intermediate between that of women without any history of glucose abnormalities and women with overt diabetes. Using data from the National Kidney Foundation''s Kidney Early Evaluation Program (KEEP), a program designed to screen participants at higher risk for CKD than the general population, we examined in cross-sectional analyses whether GDM, in the absence of subsequent overt diabetes, increases the odds of abnormal urinary albumin excretion and impaired glomerular filtration rate. In addition, we examined whether age, race, BMI, or hypertension modifies this relationship between GDM and CKD.     

Abdominal Visceral Adiposity in the First Trimester Predicts Glucose Intolerance in Later Pregnancy

OBJECTIVE

To assess whether abdominal adiposity in early pregnancy is associated with a higher risk of glucose intolerance at a later gestational stage.

RESEARCH DESIGN AND METHODS

Subcutaneous and visceral fat was measured with ultrasonography at ∼12 weeks'' gestation. A 50-g glucose challenge test (GCT) was performed between 24 and 28 weeks'' gestation. The risk of having a positive GCT (≥7.8 mmol/l) was determined in association with subcutaneous and visceral adipose tissue depths above their respective upper-quartile values relative to their bottom three quartile values.

RESULTS

Sixty-two women underwent GCTs. A visceral adipose tissue depth above the upper quartile value was significantly associated with a positive GCT in later pregnancy (adjusted odds ratio 16.9 [95% CI 1.5–194.6]). No associations were seen for subcutaneous adipose tissue.

CONCLUSIONS

Measurement of visceral adipose tissue depth in early pregnancy may be associated with glucose intolerance later in pregnancy.Maternal obesity is associated with a higher risk of gestational diabetes mellitus (GDM) (1) and adverse perinatal outcomes (2,3). Visceral adiposity (4) may better predict the onset of type 2 diabetes, independent of BMI. Given that GDM and type 2 diabetes share the same risk factors (1) and GDM predates the onset of type 2 diabetes (5), it is logical to question whether high maternal visceral adiposity is associated with GDM.We determined the reliability of first-trimester ultrasonography for measuring subcutaneous and visceral adipose tissue in pregnancy and whether either is predictive of a positive glucose challenge test (GCT), which is commonly used to screen for GDM later in pregnancy.     

Increased risk of hypertension after gestational diabetes mellitus: findings from a large prospective cohort study

OBJECTIVE

Whether a history of gestational diabetes mellitus (GDM) is associated with an increased risk of hypertension after the index pregnancy is not well established.

RESEARCH DESIGN AND METHODS

We investigated the association between GDM and subsequent risk of hypertension after the index pregnancy among 25,305 women who reported at least one singleton pregnancy between 1991 and 2007 in the Nurses’ Health Study II.

RESULTS

During 16 years of follow-up, GDM developed in 1,414 women (5.6%) and hypertension developed in 3,138. A multivariable Cox proportional hazards model showed women with a history of GDM had a 26% increased risk of developing hypertension compared with those without a history of GDM (hazard ratio 1.26 [95% CI 1.11–1.43]; P = 0.0004). These results were independent of pregnancy hypertension or subsequent type 2 diabetes.

CONCLUSIONS

These results indicate that women with GDM are at a significant increased risk of developing hypertension after the index pregnancy.Increasing evidence suggests the effect of gestational diabetes mellitus (GDM) extends beyond pregnancy for both the mother and child (1). For instance, women with a history of GDM are at a substantially higher risk of type 2 diabetes (2); small- and large-vessel vascular dysfunction (3); cardiovascular disease; and metabolic syndrome and its components, including hypertension (4–7). In the current study, we examined longitudinally whether GDM is associated with an increased risk of hypertension later in life independent of other known risk factors.     

Prepregnancy consumption of fruits and fruit juices and the risk of gestational diabetes mellitus: a prospective cohort study

OBJECTIVE

Examine the association of prepregnancy habitual consumption of fruits and fruit juices and gestational diabetes mellitus (GDM) risk.

RESEARCH DESIGN AND METHODS

A prospective study among women with at least one singleton pregnancy in the Nurses’ Health Study II from 1991 to 2001.

RESULTS

Among 13,475 women, 860 reported a first diagnosis of GDM. The adjusted relative risks (RRs) for GDM from the lowest to highest quintile of whole fruit consumption were 1.00 (referent), 0.80 (95% CI 0.65–0.98), 0.90 (0.73–1.10), 0.80 (0.64–1.00), and 0.93 (0.76–1.16), respectively. The corresponding RRs for fruit juice were 1.00, 0.82 (0.66–1.01), 0.78 (0.63–0.96), 0.84 (0.68–1.04), and 1.00 (0.81–1.23).

CONCLUSIONS

These data suggest that prepregnancy higher consumption of whole fruits is not associated with an increased GDM risk. The association between fruit juices and GDM risk appears to be nonlinear.Although dietary factors have long been recognized for their roles in the development of impaired glucose tolerance, the association between intakes of fruit and fruit juice and the risk of gestational diabetes mellitus (GDM) has yet to be investigated. The objective of this study was to assess the association of prepregnancy habitual consumption of fruit and fruit juices and their subgroups with GDM risk in a large prospective cohort of U.S. women.     

Habitually Higher Dietary Glycemic Index During Puberty Is Prospectively Related to Increased Risk Markers of Type 2 Diabetes in Younger Adulthood

OBJECTIVE

Carbohydrate nutrition during periods of physiological insulin resistance such as puberty may affect future risk of type 2 diabetes. This study examined whether the amount or the quality (dietary glycemic index [GI], glycemic load [GL], and added sugar, fiber, and whole-grain intake) of carbohydrates during puberty is associated with risk markers of type 2 diabetes in younger adulthood.

RESEARCH DESIGN AND METHODS

The analysis was based on 226 participants (121 girls and 105 boys) from the Dortmund Nutritional and Anthropometric Longitudinally Designed Study (DONALD) with an average of five 3-day weighed dietary records (range 2–6) during puberty (girls, age 9–14 years; boys, age 10–15 years) and fasting blood samples in younger adulthood (age 18–36 years) (average duration of follow-up 12.6 years). Multivariable linear regression was used to analyze the associations between carbohydrate nutrition and homeostasis model assessment–insulin resistance (HOMA-IR) as well as the liver enzymes alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) (n = 214).

RESULTS

A higher dietary GI was prospectively related to greater values of HOMA-IR (P_trend = 0.03), ALT (P_trend = 0.02), and GGT (P_trend = 0.04). After adjustment for sex, adult age, baseline BMI, and early life and socioeconomic factors as well as protein and fiber intake, predicted mean HOMA-IR values in energy-adjusted tertiles of GI were 2.37 (95% CI 2.16–2.60), 2.47 (2.26–2.71), and 2.59 (2.35–2.85). The amount of carbohydrates, GL, and added sugar, fiber, and whole-grain intake were not related to the analyzed markers.

CONCLUSIONS

Our data indicate that a habitually higher dietary GI during puberty may adversely affect risk markers of type 2 diabetes in younger adulthood.Concern has been raised that the commonly advocated low-fat, high-carbohydrate diet may be detrimental for the growing number of persons with impaired glucose tolerance even among youths, since it induces postprandial rises in glucose and insulin and may thereby increase the risk the risk of developing type 2 diabetes (1,2). Observational evidence suggests that dietary glycemic index (GI) and glycemic load (GL) are related to risk of type 2 diabetes (3,4), yet it remains to be determined whether the relevance of postprandial rises in glucose and insulin extends to puberty—a period characterized by a physiological insulin resistance (5).Chronic postprandial hyperglycemia and hyperinsulinemia can also exacerbate hepatic insulin resistance: enhanced glucose uptake by the liver subsequently leads to increased hepatic fat accumulation through upregulated de novo lipogenesis. In fact, hepatic fat accumulation is frequently observed in patients with insulin resistance or type 2 diabetes (6). The liver enzymes alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) are commonly used as surrogate parameters for hepatic fat content and are now recognized as risk markers for type 2 diabetes (7,8). Furthermore, preliminary evidence supports a role of carbohydrate nutrition for hepatic steatosis and these indirect markers of liver fat (9).This study addressed the hypothesis that recurring postprandial glycemic excursions during puberty are of specific relevance for later risk of type 2 diabetes. Since calculated dietary GI is a valid predictor of glycemic responses (10,11), we postulate that dietary GI estimated from 3-day dietary records repeatedly collected during puberty is a better predictor of type 2 diabetes risk in younger adulthood than intakes of dietary fiber, whole grain, or added sugar. This hypothesis was addressed using data from a cohort of healthy young Germans. The homeostasis model assessment–insulin resistance (HOMA-IR) index and the liver enzymes ALT and GGT was used as risk markers of type 2 diabetes.     

Determinants of insulin resistance in infants at age 1 year: impact of gestational diabetes mellitus

OBJECTIVE

The offspring of women with gestational diabetes mellitus (GDM) display a propensity for the early accrual of cardiometabolic risk factors, including insulin resistance, in childhood and adolescence. Thus, we sought to identify early life determinants of insulin resistance in infants of women with and without GDM.

RESEARCH DESIGN AND METHODS

In total, 104 full-term, singleton infants born to women with (n = 36) and without (n = 68) GDM were evaluated at age 1 year, with insulin resistance assessed by homeostasis model (HOMA-IR).

RESULTS

HOMA-IR at 1 year did not differ between infants born to mothers with and without GDM (P = 0.74). The sole independent predictor of infant HOMA-IR in the non-GDM group was birth weight (t = 3.33, P = 0.002). In contrast, weight gain in the 1st year was the only independent predictor of HOMA-IR in infants of women with GDM (t = 2.19, P = 0.039).

CONCLUSIONS

In the 1st year of life, weight gain in infants born to women with GDM is associated with insulin resistance, unlike in their peers.The offspring of women with gestational diabetes mellitus (GDM) exhibit a propensity for the early accrual of cardiometabolic risk factors in childhood and adolescence (1). Indeed, compared with their peers, offspring exposed to GDM in utero are more likely to develop insulin resistance in childhood and by as early as age 5 years (2,3). However, little is known about perinatal and early life risk factors associated with infant insulin resistance after exposure to maternal GDM. Thus, we sought to evaluate insulin resistance and its determinants in the offspring of women with and without GDM at age 1 year.     

Maternal Hyperglycemia During Pregnancy Predicts Adiposity of the Offspring

OBJECTIVE

To investigate associations between maternal pregnancy hyperglycemia, gestational diabetes mellitus (GDM), and offspring adiposity.

RESEARCH DESIGN AND METHODS

We evaluated these associations in a longitudinal study of 421 mother-daughter pairs at Kaiser Permanente Northern California. Maternal pregnancy glucose values were obtained from maternal medical records. Outcomes included three measures of girls’ adiposity, measured annually: 1) ≥85th age-specific percentile for BMI; 2) percent body fat (%BF); and 3) waist-to-height ratio (WHR).

RESULTS

Adjusting for maternal age at delivery, race/ethnicity, pregravid BMI, girl’s age, and girl’s age at onset of puberty, having a mother with GDM increased a girl’s risk of having a BMI ≥85th percentile or having %BF or WHR in the highest quartile (Q4), compared with those in the lowest quintile of blood glucose (odds ratio [OR] 3.56 [95% CI 1.28–9.92]; OR 3.13 [95% CI 1.08–9.09]; and OR 2.80 [95% CI 1.00–7.84], respectively). There was a significant interaction between the presence of GDM and pregravid BMI; girls whose mothers had both risk factors had the highest odds of having a BMI ≥85th percentile (OR 5.56 [95%CI 1.70–18.2]; Q4 %BF, OR 6.04 [95%CI 1.76–20.7]; and Q4 WHR, OR 3.60 [95%CI 1.35–9.58]). Similar, although weaker, associations were found in the association between hyperglycemia and offspring adiposity.

CONCLUSIONS

Girls who were exposed to maternal GDM or hyperglycemia in utero are at higher risk of childhood adiposity; risk increases if the mother is overweight or obese. Screening and intervention for this high-risk group is warranted to slow the intergenerational transmission of obesity and its sequelae.     

Prospective Study of Pre-Gravid Sugar-Sweetened Beverage Consumption and the Risk of Gestational Diabetes Mellitus

OBJECTIVE

Consumption of sugar-sweetened beverages (SSBs) was related to an elevated risk of type 2 diabetes and insulin resistance in several recent studies among middle- or older-aged populations. Studies on SSB consumption and glucose intolerance among pregnant women, however, are lacking. We therefore examined the association between regular SSB consumption before pregnancy and the risk of gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS

This was a prospective study among 13,475 U.S. women who reported at least one singleton pregnancy between 1992 and 2001 in the Nurses'' Health Study II. GDM was self-reported and validated by medical record review in a subsample. Cox proportional hazards models with multivariate adjustments were applied to examine the association of SSB consumption with GDM risk.

RESULTS

During 10 years of follow-up, 860 incident GDM case subjects were identified. After adjustment for age, parity, race, physical activity, smoking, alcohol intake, prepregnancy BMI, and Western dietary pattern, intake of sugar-sweetened cola was positively associated with the risk of GDM, whereas no significant association was found for other SSBs and diet beverages. Compared with women who consumed <1 serving/month, those who consumed ≥5 servings/week of sugar-sweetened cola had a 22% greater GDM risk (relative risk 1.22 [95% CI 1.01–1.47]).

CONCLUSIONS

Findings from this study suggest that prepregnancy higher consumption of sugar-sweetened cola (≥5 servings/week) is associated with an elevated GDM risk, whereas no significant association with GDM risk was observed for other SSBs and diet beverages.Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, is one of the most common pregnancy complications (1). Women with GDM are at increased risk of pregnancy complications, perinatal morbidity, and type 2 diabetes in the years after pregnancy. Offspring of women with GDM have increased risk of obesity, glucose intolerance, and diabetes in childhood and early adulthood (1). Despite the maternal and infant morbidity associated with GDM, limited attention has been paid to the identification of dietary risk factors for GDM.Sugar-sweetened beverages (SSBs) are the leading source of added sugars in Americans'' diets (2). In animal models and human studies, a high-sugar diet reduces insulin sensitivity (3,4) and insulin secretion (5). Higher consumption of SSBs was associated with an elevated risk of type 2 diabetes (6–8) and insulin resistance (9) among middle- or older-aged adults in several recent epidemiological studies. Studies regarding the impact of habitual SSB consumption on glucose intolerance among pregnant women, however, are lacking. We therefore examined the association of pregravid SSB consumption with GDM risk in a large prospective cohort of U.S. women.     

Racial/ethnic disparities in the prevalence of gestational diabetes mellitus by BMI

OBJECTIVE

To examine whether the association between gestational diabetes mellitus (GDM) and BMI category varies by racial/ethnic group.

RESEARCH DESIGN AND METHODS

In a cohort of 123,040 women without recognized pregravid diabetes who delivered babies between 1995 and 2006 at Kaiser Permanente of Northern California, we examined racial/ethnic disparities in the prevalence of GDM by BMI category and the population-attributable risk (PAR) associated with overweight/obesity.

RESULTS

Among all racial/ethnic groups, the age-adjusted prevalence of GDM increased with increasing BMI (kg/m²) category. However, Asian and Filipina women had a prevalence of GDM of 9.9 and 8.5%, respectively, at a BMI of 22.0–24.9 kg/m², whereas in Hispanic, non-Hispanic white, and African American women, the prevalence of GDM was >8.0% at a higher BMI, such as 28–30, 34–36, and ≥37 kg/m², respectively. The estimated PARs suggest that the percentage of GDM that could be prevented if all pregnant women were of normal weight (BMI <25.0 kg/m²) ranging from 65% for African American women to only 23% among Asian women.

CONCLUSIONS

Clinicians should be aware that the BMI thresholds for increased risk of GDM varies by racial/ethnic group and that the risk is high even at relatively low BMI cutoffs in Asian and Filipina women. Asian women may benefit from different prevention strategies in addition to weight management.Gestational diabetes mellitus (GDM) is carbohydrate intolerance with onset of or first recognition during pregnancy and is one of the most common pregnancy complications in the U.S. GDM is associated with increased risk for perinatal morbidity (1,2), and, in the long-term, women with GDM have an almost sevenfold increased risk of developing type 2 diabetes after pregnancy (3). The prevalence of GDM has increased in all racial/ethnic groups, and this has been observed in several populations in recent decades (4,5). Recent data suggest that the association between glucose and risk of adverse outcomes is continuous; gestational impaired glucose tolerance (IGT) is also associated with both pregnancy complications (6) and subsequent diabetes and cardiometabolic risk (7).Race/ethnicity and obesity are the two strongest independent risk factors for GDM (8–11). However, the demographic distribution of obesity (highest among African Americans and lowest among Asians) does not mirror the demographic distribution of GDM (lowest among African Americans and highest among Asians) (12). Yet there is ongoing debate surrounding the definition of overweight and obesity in Asian populations: the World Health Organization proposed a BMI cutoff of 23.0 kg/m² for overweight among Asians in 2000 (13), compared with a cutoff of 25.0 kg/m² for non-Asian populations. More recently, the World Health Organization stated that the definition of overweight in Asians likely varies depending on the outcome of interest (14). Currently, little is known about racial disparities in the risk of GDM by BMI categories.In a cohort of 123,040 women without recognized pregravid diabetes who delivered babies between 1995 and 2006 at Kaiser Permanente of Northern California (KPNC), we examined racial/ethnic disparities in the prevalence of GDM and IGT in pregnancy by BMI category and the estimated proportion of cases that could be prevented if overweight/obesity in pregnant women were eliminated (the population-attributable risk [PAR]).     

Evaluation of the Value of Fasting Plasma Glucose in the First Prenatal Visit to Diagnose Gestational Diabetes Mellitus in China

OBJECTIVE

To evaluate the value of fasting plasma glucose (FPG) value in the first prenatal visit to diagnose gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS

Medical records of 17,186 pregnant women attending prenatal clinics in 13 hospitals in China, including the Peking University First Hospital (PUFH), were examined. Patients with pre-GDM were excluded; data for FPG at the first prenatal visit and one-step GDM screening with 75-g oral glucose tolerance test (OGTT) performed between 24 and 28 weeks of gestation were collected and analyzed.

RESULTS

The median ± SD FPG value was 4.58 ± 0.437. FPG decreased with increasing gestational age. FPG level at the first prenatal visit was strongly correlated with GDM diagnosed at 24–28 gestational weeks (χ² = 959.3, P < 0.001). The incidences of GDM were 37.0, 52.7, and 66.2%, respectively, for women with FPG at the first prenatal visit between 5.10 and 5.59, 5.60 and 6.09, and 6.10–6.99 mmol/L. The data of PUFH were not statistically different from other hospitals.

CONCLUSIONS

Pregnant women (6.10 ≤ FPG < 7.00 mmol/L) should be considered and treated as GDM to improve outcomes; for women with FPG between 5.10 and 6.09 mmol/L, nutrition and exercise advice should be provided. An OGTT should be performed at 24–28 weeks to confirm or rule out GDM. Based on our data, we cannot support an FPG value ≥5.10 mmol/L at the first prenatal visit as the criterion for diagnosis of GDM.Gestational diabetes mellitus (GDM) is a one of the most common medical conditions associated with pregnancy. It was earlier defined as “hyperglycemia first recognized during pregnancy” and has more recently (2012) been described by the American Diabetes Association (ADA) as diabetes diagnosed during pregnancy that is not clearly overt diabetes (1). GDM has health consequences for both the mother and her offspring not only in the short term but also in the long term. Mothers with history of GDM have significantly higher risk of GDM during subsequent pregnancies (2) and type 2 diabetes and premature cardiovascular disease in the medium and long term, while offspring of GDM pregnancy have greater risk of developing obesity, diabetes, hypertension, cardiovascular disease, etc., in youth and adult life (3–5).The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study demonstrated that the risk of adverse maternal, fetal, and neonatal outcomes continuously increases as a function of maternal glycemia at 24–28 weeks even within ranges previously considered normal for pregnancy (6). After reviewing the results of the HAPO Study, many international diabetes study groups, including the International Association of Diabetes and Pregnancy Study Groups (IADPSG) (7) and ADA (1), have adopted the 75-g oral glucose tolerance test (OGTT) at 24–28 weeks as a screening and diagnostic test and defined new lower cutoff values for GDM diagnosis. Other studies support the new criteria (8–10). These new criteria also mean that more women will be diagnosed with GDM compared with the past; e.g., in the United Arab Emirates, more cases of GDM are diagnosed using the new standard compared with the old one (37.7 vs. 12.9%, respectively) (10). The Ministry of Health (MOH) of China published the diagnostic criteria for GDM on 1 July 2011, which have been put into effect from 1 December 2011 (11); it recommends screening with a fasting plasma glucose (FPG) test at the first prenatal visit to rule out previously undiagnosed preexisting diabetes and a 75-g OGTT between 24 and 28 weeks’ gestation for GDM diagnosis. The debate on GDM screening and diagnosis still persists in the global academic circles and professional societies; e.g., in the U.S., the American College of Obstetricians and Gynecologists continues to recommend the old diagnostic criteria of 2011 (100-g, 3-h OGTT test) (12).The possibility that women may have previously undiagnosed type 2 diabetes when they enter pregnancy is increasingly real and likely as the age of onset of type 2 diabetes keeps decreasing, whereas the age of conception keeps increasing. How to screen women at the first prenatal visit to rule out preexisting diabetes not previously known is an important issue. Performing an FPG test at first prenatal visit has been recommended for screening. The feasibility and applicability of this in low-resource settings are obvious issues (13). However, when feasible, another point of debate is the cutoff value to make the diagnosis. IADPSG and ADA have different opinions on this matter. IADPSG uses fasting glucose ≥5.10 mmol/L as the GDM diagnostic criteria at the first prenatal visit and the whole duration of pregnancy, while the ADA recommends that the first prenatal fasting glucose test only be used to identify overt diabetes (≥7.00 mmol/L) and that OGTT during the 24–28th weeks is needed for GDM screening and diagnosis. A study in 2009 reported that higher first-trimester fasting glucose increases the risk for some complications and implied that high-risk women would not get appropriate attention if the diagnosis was not made during the first prenatal visit (14). Mills et al. (15) have shown that there is physiological reduction in FPG concentration in normal pregnancy. In China, as in many other developing countries, the time for the first prenatal visit varies a lot in urban and rural settings; therefore, the value of FPG during the first prenatal visit to screen for preexisting previously undiagnosed diabetes as well as for GDM diagnosis in the first prenatal visit requires further investigation.     

Lower Adiponectin Levels at First Trimester of Pregnancy Are Associated With Increased Insulin Resistance and Higher Risk of Developing Gestational Diabetes Mellitus

OBJECTIVE

To evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, β-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women.

RESEARCH DESIGN AND METHODS

We performed anthropometric measurements and collected blood samples at 1st (6–13 weeks) and 2nd (24–28 weeks) trimesters. Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test (International Association of the Diabetes and Pregnancy Study Groups criteria). Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUC_{insulin/glucose}), and β-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay.

RESULTS

Among the 445 participants included in this study, 38 women developed GDM. Women who developed GDM had lower 1st-trimester adiponectin levels (9.67 ± 3.84 vs. 11.92 ± 4.59 µg/mL in women with normal glucose tolerance). Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1.12 per 1 µg/mL decrease of adiponectin levels; P = 0.02, adjusted for BMI and HbA_1c at 1st trimester). Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r = −0.22, P < 0.0001) and Matsuda index (r = 0.28, P < 0.0001, and r = 0.29, P < 0.0001). After adjustment for confounding factors, we found no significant association with HOMA-B and AUC_{insulin/glucose}.

CONCLUSIONS

Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements.Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition determined during pregnancy (1). In normal pregnancy, there is a progressive physiologic increase of insulin resistance, compensated by an increase of insulin secretion by pancreatic β-cells (2). Among GDM women, there is an imbalance between insulin resistance and insulin secretion capacity, resulting in increased circulating glucose levels (3). Over the past decades, GDM has drawn scientific attention because of its growing incidence and deleterious consequences for mothers and offspring (4,5). Nevertheless, the exact mechanisms implicated in its pathophysiology remain poorly understood.Adiponectin is an adipokine suspected to have insulin-sensitizing properties (6). Furthermore, lower adiponectin levels have been repeatedly and consistently associated with increased risk of type 2 diabetes incidence (7–9), but reports on GDM are inconsistent. Few studies investigated the association between adiponectin levels measured early in pregnancy and GDM incidence: some showed that low adiponectin levels are associated with increased risk of GDM (10–13), while others showed no association (14,15). Contradictory findings between studies can be partly explained by limited power and different study designs. Also, these studies inconsistently accounted for potential confounding factors like adiposity and baseline impaired glucose regulation in pregnant women. Therefore, larger prospective studies are needed, designed to take into account potential confounding factors to adequately assess whether there is an independent association between adiponectin levels and the risk of developing GDM.Thus, in the current study, we evaluated whether 1st-trimester adiponectin levels are associated with higher risk of developing GDM during pregnancy. Also, we assessed whether there is an association between adiponectin at both 1st and 2nd trimesters (or the change [Δ] over 1st to 2nd trimester) and insulin resistance/sensitivity or pancreatic β-cell function/compensation indices at 2nd trimester of pregnancy.     

Low Carbohydrate–Diet Scores and Long-term Risk of Type 2 Diabetes Among Women With a History of Gestational Diabetes Mellitus: A Prospective Cohort Study

OBJECTIVE

Low-carbohydrate diets (LCDs) may improve short-term glycemic control in patients with gestational diabetes mellitus (GDM), but the long-term effect on progression from GDM to type 2 diabetes mellitus (T2DM) is unknown. We aimed to examine the long-term risk of T2DM in association with a low-carbohydrate dietary pattern among women with a history of GDM.

RESEARCH DESIGN AND METHODS

Overall, 4,502 women with a history of GDM from the Nurses'' Health Study II (NHSII) cohort, as part of the Diabetes & Women’s Health (DWH) study, were followed up from 1991 to 2011. Overall, animal, or vegetable LCD scores, which represent adherence to different low-carbohydrate dietary patterns, were calculated using diet intake information assessed every 4 years since 1991 by validated food-frequency questionnaires. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs.

RESULTS

We documented 722 incident cases of T2DM during 68,897 person-years of observation. The multivariable-adjusted HRs (95% CIs) of T2DM, comparing the highest with lowest quintiles, were 1.36 (1.04–1.78) for overall LCD score (P = 0.003 for trend), 1.40 (1.06–1.84) for animal LCD score (P = 0.004 for trend), and 1.19 (0.91–1.55) for vegetable LCD score (P = 0.50 for trend).

CONCLUSIONS

Among women with a history of GDM, a low-carbohydrate dietary pattern, particularly with high protein and fat intake mainly from animal-source foods, is associated with higher T2DM risk, whereas a low-carbohydrate dietary pattern with high protein and fat intake from plant-source foods is not significantly associated with risk of T2DM.     

Applying Current Screening Tools for Gestational Diabetes Mellitus to a European Population: Is It Time for Change?

OBJECTIVE

The optimal screening regimen for gestational diabetes mellitus (GDM) remains controversial. Risk factors used in selective screening guidelines vary. Given that universal screening is not currently adopted in our European population, we aimed to evaluate which selective screening strategies were most applicable.

RESEARCH DESIGN AND METHODS

Between 2007 and 2009, 5,500 women were universally screened for GDM, and a GDM prevalence of 12.4% using International Association of Diabetes in Pregnancy Study Groups (IADPSG) criteria was established. We retrospectively applied selective screening guidelines to this cohort.

RESULTS

When we applied National Institute for Health and Clinical Excellence (NICE), Irish, and American Diabetes Association (ADA) guidelines, 54% (2,576), 58% (2,801), and 76% (3,656) of women, respectively, had at least one risk factor for GDM and would have undergone testing. However, when NICE, Irish, and ADA guidelines were applied, 20% (120), 16% (101), and 5% (31) of women, respectively, had no risk factor and would have gone undiagnosed. Using a BMI ≥30 kg/m² for screening has a specificity of 81% with moderate sensitivity at 48%. Reducing the BMI to ≥25 kg/m² (ADA) increases the sensitivity to 80% with a specificity of 44%. Women with no risk factors diagnosed with GDM on universal screening had more adverse pregnancy outcomes than those with normal glucose tolerance.

CONCLUSIONS

This analysis provides a strong argument for universal screening. However, if selective screening were adopted, the ADA guidelines would result in the highest rate of diagnosis and the lowest number of missed cases.The World Health Organization (WHO) defines gestational diabetes mellitus (GDM) as any degree of glucose intolerance with onset or first recognition during pregnancy (1). GDM results in higher maternal and neonatal morbidities in the short- and long-term. GDM is common, and prevalence is increasing due to the increase in overweight and obesity in the background population. In Ireland it complicates ∼12% (2) of pregnancies.Diagnosis of GDM and subsequent treatment decreases morbidities for the mother and baby in the index pregnancy. Diagnosis of GDM also highlights an at-risk population that can be targeted for primary prevention of type 2 diabetes. The optimal screening regimen for GDM remains controversial, with conflicting recommendations for universal and selective screening among various expert groups. Currently, the American Diabetes Association (ADA), the U.S. Preventive Services Task Force (USPSTF), the National Institute for Health and Clinical Excellence (NICE), and the 2010 Irish guidelines recommend risk factor–based screening. The Australasian Diabetes in Pregnancy society recommends universal screening (3). With studies from North America (4) showing that ∼90% of women have at least one risk factor for GDM, there is a strong argument for universal screening. However, a lack of randomized-controlled trials addressing this issue means there is insufficient evidence to definitely determine whether a universal approach to screening should be the gold standard of care. Also, the population of North America is phenotypically different from that of Europe, so evidence-based recommendations from North American studies may not be directly applicable to a European population.The Atlantic Diabetes in Pregnancy (ATLANTIC DIP) network is a research collaboration among five antenatal centers along the Irish Atlantic seaboard. The aim of this clinical network is to provide optimal, evidence-based care for women before, during, and after pregnancy. Between 2007 and 2009, universal screening for GDM was offered. Given that universal screening is not currently adopted or supported financially at a national level, we aimed to analyze which selective screening modalities and single risk factors had the highest sensitivity and specificity for diagnosing GDM. An additional objective was to calculate the proportion of women with GDM who would be missed if selective screening methods were adopted. Finally, there is a suggestion that women with GDM who carry no risk factors for the condition, who are only detected as part of universal screening, have a “milder” form of glucose intolerance and that their pregnancy outcomes may be similar to those of the background population. As such, this study analyzed pregnancy outcomes of these “low-risk” GDM women and compared them with the outcomes in women with normal glucose tolerance (NGT).     

Physical Activity Before and During Pregnancy and Risk of Gestational Diabetes Mellitus: A meta-analysis

OBJECTIVE

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and is associated with a substantially elevated risk of adverse health outcomes for both mothers and offspring. Physical activity may contribute to the prevention of GDM and thus is crucial for dissecting the vicious circle involving GDM, childhood obesity, and adulthood obesity, and diabetes. Therefore, we aimed to systematically review and synthesize the current evidence on the relation between physical activity and the development of GDM.

RESEARCH DESIGN AND METHODS

Medline, EMBASE, and Cochrane Reviews were searched from inception to 31 March 2010. Studies assessing the relationship between physical activity and subsequent development of GDM were included. Characteristics including study design, country, GDM diagnostic criteria, ascertainment of physical activity, timing of exposure (prepregnancy or early pregnancy), adjusted relative risks, CIs, and statistical methods were extracted independently by two reviewers.

RESULTS

Our search identified seven prepregnancy and five early pregnancy studies, including five prospective cohorts, two retrospective case-control studies, and two cross-sectional study designs. Prepregnancy physical activity was assessed in 34,929 total participants, which included 2,813 cases of GDM, giving a pooled odds ratio (OR) of 0.45 (95% CI 0.28–0.75) when the highest versus lowest categories were compared. Exercise in early pregnancy was assessed in 4,401 total participants, which included 361 cases of GDM, and was also significantly protective (0.76 [95% CI 0.70–0.83]).

CONCLUSIONS

Higher levels of physical activity before pregnancy or in early pregnancy are associated with a significantly lower risk of developing GDM.Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, affecting ∼7% of all pregnancies in the U.S. (i.e., >200,000 cases annually) (1), and this number is increasing as the prevalence of obesity among women at reproductive age escalates (2–4). GDM is associated with a significantly elevated risk for short-term and long-term complications for both mothers and offspring. Women with GDM have an increased risk for perinatal morbidity and impaired glucose tolerance and type 2 diabetes in the years after pregnancy (5,6). Children of women with GDM are more likely to be obese and have impaired glucose tolerance and diabetes in childhood and early adulthood (1). In a recent meta-analysis of randomized trials on the effect of treatment for GDM, various interventions for blood glucose control, including diet, glucose monitoring, insulin use, and pharmaceutical interventions, did not significantly reduce the risk for adverse perinatal and neonatal end points, including cesarean section and perinatal or neonatal death (7). Collectively, these data indicate that prevention of GDM altogether could be crucial for avoiding its associated adverse health outcomes.Physical activity has long been known for its role in improving glucose homeostasis through its direct or indirect impact on insulin sensitivity via several mechanisms. For instance, physical activity has independent effects on glucose disposal by increasing both insulin-mediated and non–insulin-mediated glucose disposal (8,9). Physical activity can also exert long-term effects on improvement in insulin sensitivity through increased fat-free mass (10). Furthermore, the benefits of preventing or delaying the onset of type 2 diabetes among nonpregnant individuals have been reported repeatedly (11,12). Therefore, physical activity may have the potential for preventing GDM and related adverse health outcomes. However, evidence for its impact on GDM has not been systematically synthesized. The aim of this systematic review and meta-analysis was to assemble the current evidence for the relationship between physical activity and the development of GDM.     

Diabetes Trends Among Delivery Hospitalizations in the U.S., 1994�C2004

OBJECTIVE

To examine trends in the prevalence of diabetes among delivery hospitalizations in the U.S. and to describe the characteristics of these hospitalizations.

RESEARCH DESIGN AND METHODS

Hospital discharge data from 1994 through 2004 were obtained from the Nationwide Inpatient Sample. Diagnosis codes were selected for gestational diabetes mellitus (GDM), type 1 diabetes, type 2 diabetes, and unspecified diabetes. Rates of delivery hospitalization with diabetes were calculated per 100 deliveries.

RESULTS

Overall, an estimated 1,863,746 hospital delivery discharges contained a diabetes diagnosis, corresponding to a rate of 4.3 per 100 deliveries over the 11-year period. GDM accounted for the largest proportion of delivery hospitalizations with diabetes (84.7%), followed by type 1 (7%), type 2 (4.7%), and unspecified diabetes (3.6%). From 1994 to 2004, the rates for all diabetes, GDM, type 1 diabetes, and type 2 diabetes significantly increased overall and within each age-group (15–24, 25–34, and ≥35 years) (P < 0.05). The largest percent increase for all ages was among type 2 diabetes (367%). By age-group, the greatest percent increases for each diabetes type were among the two younger groups. Significant predictors of diabetes at delivery included age ≥35 years vs. 15–24 years (odds ratio 4.80 [95% CI 4.72–4.89]), urban versus rural location (1.14 [1.11–1.17]), and Medicaid/Medicare versus other payment sources (1.29 [1.26–1.32]).

CONCLUSIONS

Given the increasing prevalence of diabetes among delivery hospitalizations, particularly among younger women, it will be important to monitor trends in the pregnant population and target strategies to minimize risk for maternal/fetal complications.Diabetes is the most frequent metabolic complication of pregnancy and is associated with an increased risk of maternal and neonatal morbidity (1,2). Most diabetes in pregnancy is gestational diabetes mellitus (GDM). Depending on the population, GDM affects up to 14% of pregnancies, although most commonly reported figures range from 2 to 5% (3,4). With the rapid rise of type 2 diabetes among women in general, it is expected that this condition will also affect pregnant women at an increasing rate.A number of studies have reported increasing trends for pregestational diabetes, GDM, or both (5–7). The majority of these results, however, generally describe diabetes patterns at more localized levels in the U.S. Studies that have assessed diabetes trends in pregnancy at the national level have done so with a specific focus only on GDM, reporting marked increases in prevalence over the past 2 decades (8,9).As a comparison to these previously reported numbers and for a more comprehensive assessment of diabetes in pregnancy in the U.S., the purpose of this analysis was to examine trends and characteristics of delivery hospitalizations with a recorded diabetes diagnosis of GDM, type 1 diabetes, and type 2 diabetes between 1994 and 2004 using the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS), a nationally representative sample of inpatient care. Given the rising background rates of type 2 diabetes, together with increases in risk factors for diabetes, which may be contributing to the trends in the general population, we expected that trends among pregnant women, particularly for GDM and type 2 diabetes, would also steadily increase, reflecting the patterns reported in localized studies.     

Postpartum Diabetes Screening: Adherence rate and the performance of fasting plasma glucose versus oral glucose tolerance test

OBJECTIVE

To determine the rate of adherence to postpartum glycemic testing in women with gestational diabetes mellitus (GDM) and the performance of fasting plasma glucose (FPG) versus the 75-g oral glucose tolerance test (OGTT) in detecting postpartum glucose intolerance.

RESEARCH DESIGN AND METHODS

The study was a retrospective cohort of 1,006 women with GDM attending a pregnancy diabetes clinic.

RESULTS

Postpartum screening was completed in 438 (48%) women. Women nonadherent to testing had higher parity (1.10 vs. 0.87) and were less likely to require insulin for management of their GDM. Among women who were tested, 89 (21%) had an abnormal result, only 25 (28%) of whom were identified by FPG. Factors associated with abnormal postpartum diabetes screening include non-Caucasian ethnicity, previous GDM, higher A1C, and OGTT values during pregnancy and treatment with insulin.

CONCLUSIONS

The rate of postpartum diabetes screening is low, and FPG lacks sensitivity as a screening test in comparison with OGTT.Gestational diabetes mellitus (GDM) strongly predicts future development of type 2 diabetes (1), and abnormal glucose tolerance can persist postpartum leading to impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (2). Compared with an oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) has greater reproducibility but may lack sensitivity to identify women with IGT or type 2 diabetes (3–5). The main study objectives were to assess adherence with postpartum testing, to identify factors associated with nonadherence, and to compare the sensitivity of FPG versus a 75-g OGTT in detecting postpartum glucose intolerance.     

ATLANTIC DIP: The Impact of Obesity on Pregnancy Outcome in Glucose-Tolerant Women

OBJECTIVE

A prospective study of the impact of obesity on pregnancy outcome in glucose-tolerant women.

RESEARCH DESIGN AND METHODS

The Irish Atlantic Diabetes in Pregnancy network advocates universal screening for gestational diabetes. Women with normoglycemia and a recorded booking BMI were included. Maternal and infant outcomes correlated with booking BMI are reported.

RESULTS

A total of 2,329 women fulfilled the criteria. Caesarean deliveries increased in overweight (OW) (odds ratio 1.57 [95% CI 1.24–1.98]) and obese (OB) (2.65 [2.03–3.46]) women. Hypertensive disorders increased in OW (2.30 [1.55–3.40]) and OB (3.29 [2.14–5.05]) women. Reported miscarriages increased in OB (1.4 [1.11–1.77]) women. Mean birth weight was 3.46 kg in normal BMI (NBMI), 3.54 kg in OW, and 3.62 kg in OB (P < 0.01) mothers. Macrosomia occurred in 15.5, 21.4, and 27.8% of babies of NBMI, OW, and OB mothers, respectively (P < 0.01). Shoulder dystocia occur in 4% (>4 kg) compared with 0.2% (<4 kg) babies (P < 0.01). Congenital malformation risk increased for OB (2.47 [1.09–5.60]) women.

CONCLUSIONS

OW and OB glucose-tolerant women have greater adverse pregnancy outcomes.Obesity is now a global pandemic (1) and increases the risk of gestational diabetes mellitus (GDM). Few studies (2,3) have examined the independent effects of obesity on pregnancy outcome in glucose-tolerant women.     

Lipoprotein Particles and Incident Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis

OBJECTIVE

In the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated associations of baseline levels of a lipoprotein-based insulin resistance (IR) index (LP-IR), IR-related lipoprotein particles, mean particle sizes, and lipids, with incident type 2 diabetes, independent of confounders, glucose, insulin, and HOMA-IR.

RESEARCH DESIGN AND METHODS

Among 5,314 adults aged 45–84 years without baseline diabetes or cardiovascular disease, 656 cases of diabetes were identified during a mean follow-up of 7.7 years. Lipoprotein particle concentrations, size, and LP-IR were determined by nuclear magnetic resonance spectroscopy of stored baseline plasma. Potential effect modification, by race/ethnicity, sex, baseline use of lipid-lowering medications or hormone therapy, or glucose strata (<90, 90–99, and ≥100 mg/dL), was also evaluated.

RESULTS

Higher levels of LP-IR, large VLDL particles (VLDL-P), small LDL particles, triglycerides (TG), and TG–to–HDL cholesterol (HDL-C) ratio and lower levels of large HDL particles, smaller HDL and LDL size, and larger VLDL size were significantly associated with incident diabetes adjusted for confounders and glucose or insulin. These also were similar by race/ethnicity, sex, and treatment group. Associations were similar for LP-IR, large VLDL-P, mean VLDL size, TG, and TG–to–HDL-C ratio; they persisted for LP-IR, large VLDL-P, or mean VLDL size adjusted for HOMA-IR or TG–to–HDL-C ratio and glucose but not for the TG–to–HDL-C ratio adjusted for LP-IR or for HOMA-IR or insulin if adjusted for LP-IR and glucose.

CONCLUSIONS

Among ethnically diverse men and women, LP-IR, large VLDL-P, large VLDL size, TG, and TG–to–HDL-C ratio were associated with incident diabetes independent of established risk factors, glucose, insulin, or HOMA-IR, as well as the use of lipid-lowering medications or hormone therapy.