Improving the care of women with gestational diabetes

The article reviews gestational diabetes mellitus, including etiology, diagnostic and screening criteria, risk factors, and care of the affected woman. Gestational diabetes mellitus affects approximately 7% of all pregnant women, resulting in more than 200,000 cases each year, and is defined as glucose intolerance that begins or is first recognized during pregnancy. Women are considered at high risk for gestational diabetes if they are markedly obese, have a personal history of gestational diabetes, have a strong family history of diabetes, or have glycosuria. Risk assessment is essential in determining whether a woman should be screened or tested for gestational diabetes. Women who have had gestational diabetes should have comprehensive preconception care prior to a subsequent pregnancy to ascertain appropriate weight, nutrition, exercise, and signs of gestational diabetes.     

Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study

OBJECTIVETo investigate the association of folate and vitamin B₁₂ in early pregnancy with gestational diabetes mellitus (GDM) risk.RESEARCH DESIGN AND METHODSThe data of this study were from a subcohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B₁₂ measurements at recruitment (between 9 and 13 gestational weeks) and those with three samples available for glucose measurements under an oral glucose tolerance test. GDM was diagnosed between 24 and 28 weeks’ gestation. Odds ratio (OR) and 95% CI of having GDM was used to quantify the association.RESULTSA total of 1,058 pregnant women were included, and GDM occurred in 180 (17.01%). RBC folate and vitamin B₁₂ were significantly higher in pregnancies with GDM than those without GDM (P values were 0.045 and 0.002, respectively) and positively correlated with 1-h and 2-h serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM; OR (95% CI) was 1.73 (1.19–2.53) (P = 0.004). Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ≥600 ng/mL were associated with ∼1.60-fold higher odds of GDM; the adjusted OR (95% CI) was 1.58 (1.03–2.41) (P = 0.033). A significant trend of risk effect on GDM risk across categories of RBC folate was observed (P_trend = 0.021). Vitamin B₁₂ was significantly associated with GDM risk (OR 1.14 per 100 pg/mL; P = 0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B₁₂ with GDM was observed.CONCLUSIONSHigher maternal RBC folate and vitamin B₁₂ levels in early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B₁₂ is not significantly associated with GDM.     

Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY)

OBJECTIVEWhile it is known that there is progression to diabetes in <10 years in 70% of children with two or more islet autoantibodies, predictors of the progression to diabetes are only partially defined.RESULTSLife table analysis revealed that the cumulative incidence of diabetes by 5 years since the appearance of the first autoantibody differed significantly by the number of positive autoantibodies (47%, 36%, and 11%, respectively, in those with three autoantibodies, two autoantibodies, and one autoantibody, P < 0.001). In time-varying survival models adjusted for first-degree relative status, number of autoantibodies, age at first persistent confirmed autoantibodies, and HLA genotypes, higher mean IAA and IA-2A levels were associated with an increased risk of type 1 diabetes in children who were persistently autoantibody positive (IAAs: hazard ratio [HR] 8.1 [95% CI 4.6–14.2]; IA-2A: HR 7.4 [95% CI 4.3–12.6]; P < 0.0001]). The mean GADA level did not significantly affect the risk of diabetes.CONCLUSIONSIn the TEDDY study, children who have progressed to diabetes usually expressed two or more autoantibodies. Higher IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive.     

Metabolomics and Type 2 Diabetes Risk: An Updated Systematic Review and Meta-analysis of Prospective Cohort Studies

BACKGROUNDDue to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted.PURPOSETo conduct an updated systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes.DATA SOURCESWe searched PubMed and Embase until 6 March 2021.STUDY SELECTIONWe selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes.DATA EXTRACTIONBaseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies.DATA SYNTHESISA total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate–corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07–2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69–0.90).LIMITATIONSSubstantial heterogeneity (I² > 50%, τ² > 0.1) was observed for some of the metabolites.CONCLUSIONSSeveral plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.     

Remnant Cholesterol and Its Visit-to-Visit Variability Predict Cardiovascular Outcomes in Patients With Type 2 Diabetes: Findings From the ACCORD Cohort

OBJECTIVERemnant cholesterol (remnant-C) predicts atherosclerotic cardiovascular disease, regardless of LDL-cholesterol (LDL-C) levels. This study assessed the associations between remnant-C and cardiovascular outcomes in type 2 diabetes.RESEARCH DESIGN AND METHODSThis post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial used patient (type 2 diabetes >3 months) remnant-C and major adverse cardiovascular event (MACE) data from the study database. The associations between remnant-C and MACEs were evaluated using Cox proportional hazards regression analyses. We examined the relative MACE risk in remnant-C versus LDL-C discordant/concordant groups using clinically relevant LDL-C targets by discordance analyses.RESULTSThe baseline analysis included 10,196 participants, with further visit-to-visit variability analysis including 9,650 participants. During follow-up (median, 8.8 years), 1,815 patients (17.8%) developed MACEs. After adjusting for traditional cardiovascular risk factors, each 1-SD increase in remnant-C was associated with a 7% higher MACE risk (hazard ratio [HR] 1.07, 95% CI 1.02–1.12, P = 0.004). In the fully adjusted model, the visit-to-visit remnant-C variability calculated using logSD (HR 1.41, 95% CI 1.18–1.69, P < 0.001) and logARV (HR 1.45, 95% CI 1.22–1.73, P < 0.001) was associated with MACEs. Residual lipid risk (remnant-C ≥31 mg/dL) recognized individuals at a higher MACE risk, regardless of LDL-C concentrations. Within each LDL-C subgroup (>100 or ≤100 mg/dL), high baseline remnant-C was associated with a higher MACE risk (HR 1.37, 95% CI 1.09–1.73, P = 0.007; HR 1.22, 95% CI 1.04–1.41, P = 0.015, respectively).CONCLUSIONSRemnant-C levels were associated with MACEs in patients with type 2 diabetes independent of LDL-C, and visit-to-visit remnant-C variability helped identify those with higher cardiovascular risk.     

Maternal and Neonatal Circulating Markers of Metabolic and Cardiovascular Risk in the Metformin in Gestational Diabetes (MiG) Trial: Responses to maternal metformin versus insulin treatment

OBJECTIVE

This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated with metformin or insulin and in cord plasma of their offspring and to examine how these markers relate to infant size at birth.

RESEARCH DESIGN AND METHODS

Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial. Fasting maternal plasma glucose, lipids, and CRP were measured at randomization, 36 weeks’ gestation, and 6–8 weeks postpartum as well as in cord plasma. Women with available cord blood samples (metformin n = 236, insulin n = 242) were included.

RESULTS

Maternal plasma triglycerides increased more from randomization to 36 weeks’ gestation in women treated with metformin (21.93%) versus insulin (9.69%, P < 0.001). Maternal and cord plasma lipids, CRP, and neonatal anthropometry did not differ between treatments. In logistic regression analyses adjusted for confounders, the strongest associations with birth weight >90th centile were maternal triglycerides and measures of glucose control at 36 weeks.

CONCLUSIONS

There were few differences in circulating maternal and neonatal markers of metabolic status and no differences in measures of anthropometry between the offspring of women treated with metformin and the offspring of women treated with insulin. There may be subtle effects of metformin on maternal lipid function, but the findings suggest that treating gestational diabetes mellitus with metformin does not adversely affect lipids or CRP in cord plasma or neonatal anthropometric measures.Gestational diabetes mellitus is carbohydrate intolerance first diagnosed during pregnancy (1) and affects up to 18% of pregnancies. The prevalence varies depending on maternal demographics and diagnostic criteria (2). The prevalence of gestational diabetes mellitus is increasing, which is likely driven by the rising population prevalence of overweight and obesity and increasing maternal age at pregnancy (3). Gestational diabetes mellitus increases maternal and infant morbidity and mortality during pregnancy (4). Women with a history of gestational diabetes mellitus are at risk for metabolic syndrome, type 2 diabetes (5), and cardiovascular disease in later life (6). Children born to women with gestational diabetes mellitus have higher rates of type 2 diabetes and obesity (7).Treating gestational diabetes mellitus improves pregnancy outcomes for both mother and infant (8). Current therapies include modification of diet, increased physical activity, and drug therapy with insulin and oral hypoglycemic agents, including metformin. In addition to improving insulin sensitivity and hyperglycemia, metformin therapy in the setting of type 2 diabetes reduces triglycerides (9), total cholesterol, LDL cholesterol (10), and VLDL cholesterol; increases HDL cholesterol (9); and reduces markers of inflammation and thrombosis (11). Metformin therapy in gestational diabetes mellitus achieves maternal glucose control and pregnancy outcomes similar to insulin therapy (12,13).In contrast to insulin, metformin crosses the placenta (14) and, therefore, could directly influence fetal metabolism. Our recent follow-up studies in 2-year-old offspring of women enrolled in the Metformin in Gestational Diabetes (MiG) trial showed increased subcutaneous fat measurements with no increase in abdominal adiposity or total fat (15). Further assessments are required to determine whether metformin actually reduces visceral/ectopic fat. Therefore, we hypothesized that metformin would be more effective than insulin in improving markers of insulin sensitivity and cardiovascular risk during pregnancy and postpartum in women with gestational diabetes mellitus and in their newborns.     

Relationship Between Parental Diabetes and Presentation of Metabolic and Glycemic Function in Youth With Type 2 Diabetes: Baseline Findings From the TODAY Trial

OBJECTIVE

Children whose parents have diabetes are at increased risk for developing type 2 diabetes. This report assessed relationships between parental diabetes status and baseline demographics, anthropometrics, metabolic measurements, insulin sensitivity, and β-cell function in children recently diagnosed with type 2 diabetes.

RESEARCH DESIGN AND METHODS

The sample included 632 youth (aged 10–17 years) diagnosed with type 2 diabetes for <2 years who participated in the TODAY clinical trial. Medical history data were collected at baseline by self-report from parents and family members. Youth baseline measurements included an oral glucose tolerance test and other measures collected by trained study staff.

RESULTS

Youth exposed to maternal diabetes during pregnancy (whether the mother was diagnosed with diabetes prior to pregnancy or had gestational diabetes mellitus) were diagnosed at younger ages (by 0.6 years on average), had greater dysglycemia at baseline (HbA_1c increased by 0.3% [3.4 mmol/mol]), and had reduced β-cell function compared with those not exposed (C-peptide index 0.063 vs. 0.092). The effect of maternal diabetes on β-cell function was observed in non-Hispanic blacks and Hispanics but not whites. Relationships with paternal diabetes status were minimal.

CONCLUSIONS

Maternal diabetes prior to or during pregnancy was associated with poorer glycemic control and β-cell function overall but particularly in non-Hispanic black and Hispanic youth, supporting the hypothesis that fetal exposure to aberrant metabolism may have long-term effects. More targeted research is needed to understand whether the impact of maternal diabetes is modified by racial/ethnic factors or whether the pathway to youth-onset type 2 diabetes differs by race/ethnicity.     

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.     

Pregravid Liver Enzyme Levels and Risk of Gestational Diabetes Mellitus During a Subsequent Pregnancy

OBJECTIVE

Liver enzymes are independent predictors of type 2 diabetes. Although liver fat content correlates with features of insulin resistance, a risk factor for developing gestational diabetes mellitus (GDM), the relationship between liver enzymes and GDM is unclear. The objective of this study was to assess whether pregravid liver enzyme levels are associated with subsequent risk of GDM.

RESEARCH DESIGN AND METHODS

A nested case-control study was conducted among women who participated in the Kaiser Permanente Northern California multiphasic health checkup (1984–1996) and had a subsequent pregnancy (1984–2009). Case patients were 256 women who developed GDM. Two control subjects were selected for each case patient and matched for year of blood draw, age at examination, age at pregnancy, and number of intervening pregnancies.

RESULTS

Being in the highest quartile versus the lowest quartile of γ-glutamyl transferase (GGT) levels was associated with a twofold increased risk of subsequent GDM (odds ratio 1.97 [95% CI 1.14–3.42]), after adjusting for race/ethnicity, prepregnancy BMI, family history of diabetes, and alcohol use. This result was attenuated after adjusting for homeostasis model assessment of insulin resistance (HOMA-IR), fasting status, and rate of gestational weight gain. There was significant interaction between GGT and HOMA-IR; the association with GGT was found among women in the highest tertile of HOMA-IR. Aspartate aminotransferase and alanine aminotransferase were not associated with increased GDM risk.

CONCLUSIONS

Pregravid GGT level, but not alanine aminotransferase or aspartate aminotransferase level, predicted the subsequent risk of GDM. Markers of liver fat accumulation, such as GGT level, are present years before pregnancy and may help to identify women at increased risk for subsequent GDM.     

Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment

OBJECTIVEIn observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor.RESEARCH DESIGN AND METHODSIn the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data.RESULTSAmong 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02−1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85–1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment–baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03−1.12; P = 0.0002) for incident type 2 diabetes.CONCLUSIONSIn patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.     

American Diabetes Association Framework for Glycemic Control in Older Adults: Implications for Risk of Hospitalization and Mortality

OBJECTIVEThe 2021 American Diabetes Association (ADA) guidelines recommend different A1C targets in older adults that are based on comorbid health status. We assessed risk of mortality and hospitalizations in older adults with diabetes across glycemic control (A1C <7%, 7 to <8%, ≥8%) and ADA-defined health status (healthy, complex/intermediate, very complex/poor) categories.RESEARCH DESIGN AND METHODSProspective cohort analysis of older adults aged 66–90 years with diagnosed diabetes in the Atherosclerosis Risk in Communities (ARIC) study.RESULTSOf the 1,841 participants (56% women, 29% Black), 32% were classified as healthy, 42% as complex/intermediate, and 27% as very complex/poor health. Over a median 6-year follow-up, there were 409 (22%) deaths and 4,130 hospitalizations (median [25th–75th percentile] 1 per person [0–3]). In the very complex/poor category, individuals with A1C ≥8% (vs. <7%) had higher mortality risk (hazard ratio 1.76 [95% CI 1.15–2.71]), even after adjustment for glucose-lowering medication use. Within the very complex/poor health category, individuals with A1C ≥8% (vs. <7%) had more hospitalizations (incidence rate ratio [IRR] 1.41 [95% CI 1.03–1.94]). In the complex/intermediate group, individuals with A1C ≥8% (vs. <7%) had more hospitalizations, even with adjustment for glucose-lowering medication use (IRR 1.64 [1.21–2.24]). Results were similar, but imprecise, when the analysis was restricted to insulin or sulfonylurea users (n = 663).CONCLUSIONSThere were substantial differences in mortality and hospitalizations across ADA health status categories, but older adults with A1C <7% were not at elevated risk, regardless of health status. Our results support the 2021 ADA guidelines and indicate that <7% is a reasonable treatment goal in some older adults with diabetes.     

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.     

Type 2 Diabetes Subgroups,Risk for Complications,and Differential Effects Due to an Intensive Lifestyle Intervention

OBJECTIVEWe reevaluated the Action for Health in Diabetes (Look AHEAD) intervention, incorporating diabetes subgroups, to identify whether intensive lifestyle intervention (ILI) is associated with differential risk for cardiovascular disease (CVD) by diabetes subgroup.RESEARCH DESIGN AND METHODSIn the Look AHEAD trial, 5,145 participants, aged 45–76 years, with type 2 diabetes (T2D) and overweight or obesity were randomly assigned to 10 years of ILI or a control condition of diabetes support and education. The ILI focused on weight loss through decreased caloric intake and increased physical activity. To characterize diabetes subgroups, we applied k-means clustering to data on age of diabetes diagnosis, BMI, waist circumference, and glycated hemoglobin. We examined whether relative intervention effects on the trial’s prespecified CVD outcomes varied among diabetes subgroups.RESULTSWe characterized four subgroups related to older age at diabetes onset (42% of sample), poor glucose control (14%), severe obesity (24%), and younger age at diabetes onset (20%). We observed interactions (all P < 0.05) between intervention and diabetes subgroups for three separate composite cardiovascular outcomes. Randomization to ILI was associated with increased risk for each cardiovascular outcome only among the poor-glucose-control subgroup (hazard ratio >1.32). Among the three other diabetes subgroups, ILI was not associated with increased risk for CVD.CONCLUSIONSAmong overweight and obese adults with T2D, a lifestyle intervention was associated with differential risk for CVD that was dependent on diabetes subgroup. Diabetes subgroups may be important to identify the patients who would achieve benefit and avoid harm from an ILI.     

自然受孕与辅助生殖受孕妊娠期糖尿病患者围生期结局的回顾性队列研究

目的 比较不同受孕方式的妊娠期糖尿病患者围生期结局。方法 选取2015年2月—2018年2月在本院分娩的的1 839例妊娠期糖尿病患者资料进行回顾性队列研究,其中辅助生殖组298例,自然受孕组1 541例,比较2组间母婴围生期结局。结果 与自然受孕组相比,辅助生殖组孕妇年龄偏高,超重率偏低,差异有统计学差异（P<0.05）。辅助生殖组孕妇妊娠期高血压、严重子〗前期、剖宫产以及早产发生率高于自然妊娠组,差异有统计学意义（P<0.05）。结论 通过辅助生殖受孕的妊娠期糖尿病患者妊娠期高血压、严重子〗前期、剖宫产以及早产等不良分娩结局风险增加。     

High Calorie Intake Is Associated With Worsening Insulin Resistance and β-Cell Function in Hispanic Women After Gestational Diabetes Mellitus

OBJECTIVETo assess associations between dietary intake and rates of change in insulin resistance and β-cell function in Hispanic women with prior gestational diabetes mellitus (GDM).RESULTSThe median length of follow-up from the first postpartum evaluation was 8.0 years (interquartile range 4.5–10.8 years). At baseline, women were 32 ± 5.7 years old and had a median calorie intake of 2,091 kcal/day. Over the course of follow-up, dietary intake did not change significantly. Higher baseline calorie intake was associated with a faster decline in insulin sensitivity, measured by the insulin sensitivity index (S_I) (P = 0.029), and β-cell compensation, measured by the disposition index (DI) (P = 0.027), over time. These associations remained after adjustment for baseline characteristics; changes in BMI, calorie intake, levels of physical activity; and additional pregnancies during the follow-up period. The median rates were −0.06 vs. −0.02 units/year for S_I and −810 vs. −692 units/year for DI for women with baseline calorie intake above versus below the cohort median.CONCLUSIONSHigh calorie intake is associated with a faster decline in insulin sensitivity and β-cell compensation in Hispanic women who are at high risk for type 2 diabetes, independent of adiposity.     

Alcohol Abstinence and the Risk of Atrial Fibrillation in Patients With Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide Population-Based Study

OBJECTIVETo investigate the effects of alcohol abstinence on prevention of new-onset atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODSA total of 1,112,682 patients newly diagnosed with T2DM between 2011 and 2014 were identified from the Korean National Health Insurance Service database. After excluding those with a history of AF, 175,100 patients were included. The primary outcome was new-onset AF.RESULTSDuring a mean follow-up of 4.0 years, AF occurred in 4,174 patients. Those with heavy alcohol consumption (alcohol intake ≥40 g/day) before T2DM diagnosis had a higher risk of AF (adjusted hazard ratio [aHR] 1.22; 95% CI 1.06–1.41) compared with patients with no alcohol consumption. After T2DM diagnosis, those with moderate to heavy alcohol consumption (alcohol intake ≥20 g/day) who abstained from alcohol had a lower risk of AF (aHR 0.81; 95% CI 0.68–0.97) compared with constant drinkers. Alcohol abstinence showed consistent trends toward lower incident AF in all subgroups and was statistically significant in men (aHR 0.80; 95% CI 0.67–0.96), those aged >65 years (aHR 0.69; 95% CI 0.52–0.91), those with CHA₂DS₂-VASc score <3 points (aHR 0.71; 95% CI 0.59–0.86), noninsulin users (aHR 0.77; 95% CI 0.63–0.94), and those with BMI <25 kg/m² (aHR 0.68; 95% CI 0.53–0.88).CONCLUSIONSIn patients with newly diagnosed T2DM, alcohol abstinence was associated with a low risk of AF development. Lifestyle modifications, such as alcohol abstinence, in patients newly diagnosed with T2DM should be recommended to reduce the risk of AF.     

Risk Factors for Incident Fracture in Older Adults With Type 2 Diabetes: The Framingham Heart Study

OBJECTIVETo identify risk factors for fracture in type 2 diabetes.RESEARCH DESIGN AND METHODSThis prospective study included members of the Framingham Original and Offspring Cohorts. Type 2 diabetes was defined as fasting plasma glucose >125 mg/dL or use of type 2 diabetes therapy. We used repeated-measures Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% CIs for associations between potential predictors and incidence of fragility fracture.RESULTSParticipants included 793 individuals with type 2 diabetes. Mean ± SD age was 70 ± 10 years; 45% were women. A total of 106 incident fractures occurred over 1,437 observation follow-up intervals. Fracture incidence increased with age (adjusted HRs 1.00, 1.44 [95% CI 0.65, 3.16], and 2.40 [1.14, 5.04] for <60, 60–70, and >70 years, respectively; P_trend = 0.02), female sex (2.23 [1.26, 3.95]), HbA_1c (1.00, 2.10 [1.17, 3.75], and 1.29 [0.69, 2.41] for 4.45–6.46% [25–47 mmol/mol], 6.50–7.49% [48–58 mmol/mol], and 7.50–13.86% [58–128 mmol/mol]; P_trend =0.03), falls in past year (1.00, 1.87 [0.82, 4.28], and 3.29 [1.34, 8.09] for no falls, one fall, and two or more falls; P_trend =0.03), fracture history (2.05 [1.34, 3.12]), and lower grip strength (0.82 [0.69, 0.99] per 5-kg increase). Femoral neck bone mineral density, BMI, smoking, physical function, chronic diseases, medications, and physical function were not associated with fracture incidence.CONCLUSIONSPrior falls, fractures, low grip strength, and elevated HbA_1c are risk factors for fractures in older adults with type 2 diabetes. Evaluation of these factors may improve opportunities for early intervention and reduce fractures in this high-risk group.     

Case Fatality of Patients With Type 1 Diabetes After Myocardial Infarction

OBJECTIVEType 1 diabetes is a risk factor for myocardial infarction (MI). We aimed to evaluate the case fatality in patients with type 1 diabetes after MI.RESEARCH DESIGN AND METHODSConsecutive patients experiencing MI with type 1 diabetes (n = 1,935; 41% female; mean age 62.5 years) and without diabetes (n = 74,671) admitted to 20 hospitals in Finland from 2005 to 2018 were studied using national registries. The outcome of interest was death within 1 year after MI. Differences between groups were balanced by multivariable adjustments and propensity score matching.RESULTSCase fatality was higher in patients with type 1 diabetes than in propensity score–matched controls without diabetes at 30 days (12.8% vs. 8.5%) and at 1 year (24.3% vs. 16.8%) after MI (hazard ratio 1.55; 95% CI 1.32–1.81; P < 0.0001). Patients with type 1 diabetes had poorer prognosis in subgroups of men and women and of those with and without ST-elevation MI, with and without revascularization, with and without atrial fibrillation, and with and without heart failure. The relative fatality risk in type 1 diabetes was highest in younger patients. Older age, heart failure, peripheral vascular disease, renal failure, and no revascularization were associated with worse prognosis after MI. The case fatality among patients with type 1 diabetes decreased during the study period, but outcome differences compared with patients without diabetes remained similar.CONCLUSIONSPatients with type 1 diabetes are at higher risk of death after MI than patients without diabetes. Our findings call for attention to vigorous cardiovascular disease prevention in patients with type 1 diabetes.     

Changes in Plant-Based Diet Indices and Subsequent Risk of Type 2 Diabetes in Women and Men: Three U.S. Prospective Cohorts

OBJECTIVEWe evaluated the associations between changes in plant-based diets and subsequent risk of type 2 diabetes.RESEARCH DESIGN AND METHODSWe prospectively followed 76,530 women in the Nurses’ Health Study (NHS) (1986–2012), 81,569 women in NHS II (1991–2017), and 34,468 men in the Health Professionals Follow-up Study (1986–2016). Adherence to plant-based diets was assessed every 4 years with the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs). We pooled results of the three cohorts using meta-analysis.RESULTSWe documented 12,627 cases of type 2 diabetes during 2,955,350 person-years of follow-up. After adjustment for initial BMI and initial and 4-year changes in alcohol intake, smoking, physical activity, and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest decrease (>10%) in PDI and hPDI over 4 years had a 12–23% higher diabetes risk in the subsequent 4 years (pooled HR, PDI 1.12 [95% CI 1.05, 1.20], hPDI 1.23 [1.16, 1.31]). Each 10% increment in PDI and hPDI over 4 years was associated with a 7–9% lower risk (PDI 0.93 [0.91, 0.95], hPDI 0.91 [0.87, 0.95]). Changes in uPDI were not associated with diabetes risk. Weight changes accounted for 6.0–35.6% of the associations between changes in PDI and hPDI and diabetes risk.CONCLUSIONSImproving adherence to overall and healthful plant-based diets was associated with a lower risk of type 2 diabetes, whereas decreased adherence to such diets was associated with a higher risk.