OBJECTIVETo report frequencies of gestational diabetes mellitus (GDM) among the 15 centers that participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study using the new International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria.RESEARCH DESIGN AND METHODSAll participants underwent a 75-g oral glucose tolerance test between 24 and 32 weeks’ gestation. GDM was retrospectively classified using the IADPSG criteria (one or more fasting, 1-h, or 2-h plasma glucose concentrations equal to or greater than threshold values of 5.1, 10.0, or 8.5 mmol/L, respectively).RESULTSOverall frequency of GDM was 17.8% (range 9.3–25.5%). There was substantial center-to-center variation in which glucose measures met diagnostic thresholds.CONCLUSIONSAlthough the new diagnostic criteria for GDM apply globally, center-to-center differences occur in GDM frequency and relative diagnostic importance of fasting, 1-h, and 2-h glucose levels. This may impact strategies used for the diagnosis of GDM.

Efficacy and safety of the glucagon-like peptide 1 (GLP-1) analog oral semaglutide and the sodium-glucose cotransporter 2 inhibitor empagliflozin were compared in patients with type 2 diabetes uncontrolled on metformin. RESEARCH DESIGN AND METHODS Patients were randomized to once-daily open-label treatment with oral semaglutide 14 mg (n 5 412) or empagliflozin 25 mg (n 5 410) in a 52-week trial. Key end points were change from baseline to week 26 in HbA 1c (primary) and body weight (confirmatory secondary). Two estimands addressed efficacy-related questions: treatment policy (regardless of trial product discontinuation or rescue medication) and trial product (on trial product without rescue medication) in all randomized patients. RESULTS Four hundred (97.1%) patients in the oral semaglutide group and 387 (94.4%) in the empagliflozin group completed the trial. Oral semaglutide provided superior reductions in HbA 1c versus empagliflozin at week 26 (treatment policy-1.3% vs.-0.9% [-14 vs.-9 mmol/mol], estimated treatment difference [ETD]-0.4% [95% CI-0.6,-0.3] [-5 mmol/mol (-6,-3)]; P < 0.0001). The treatment difference in HbA 1c significantly favored oral semaglutide at week 26 for the trial product estimand (-1.4% vs.-0.9% [-15 vs.-9 mmol/mol], ETD-0.5% [95% CI-0.7,-0.4] [-6 mmol/mol (-7,-5)]; P < 0.0001) and at week 52 for both estimands (P < 0.0001). Superior weight loss was not confirmed at week 26 (treatment policy), but oral semaglutide was significantly better than empagliflozin at week 52 (trial product 24.7 vs. 23.8 kg; P 5 0.0114). Gastrointestinal adverse events were more common with oral semaglutide. CONCLUSIONS Oral semaglutide was superior to empagliflozin in reducing HbA 1c but not body weight at 26 weeks in patients with type 2 diabetes uncontrolled on metformin. At week 52, HbA 1c and body weight (trial product estimand) were significantly reduced versus empagliflozin. Oral semaglutide was well tolerated within the established safety profile of GLP-1 receptor agonists.

Among women with GD identified by contemporary criteria compared with those without it, GD was significantly associated with a higher maternal risk for a disorder of glucose metabolism during long-term follow-up after pregnancy. Among children of mothers with GD vs those without it, the difference in childhood overweight or obesity defined by body mass index cutoffs was not statistically significant; however, additional measures of childhood adiposity may be relevant in interpreting the study findings.

To determine the effects of continuous aerobic exercise training (CON) vs interval aerobic exercise training (INT) on glycemic control and endothelium-dependent vasodilatation, 43 participants with type 2 diabetes were randomly allocated to the sedentary, CON, and INT groups. The CON and INT exercise training programs were designed to yield the same energy expenditure/exercise session and included walking on treadmill for 30 and 40 min/day, 3 times/week for 12 weeks. Body fatness and heart rate at rest decreased and leg muscle strength increased (all P < 0.05) in both the CON and INT groups. Fasting blood glucose levels decreased (P < 0.05) in both exercise groups but glycosylated hemoglobin levels decreased (P < 0.05) only in the INT group. Maximal aerobic capacity, flow-mediated dilation, and cutaneous reactive hyperemia increased significantly in both exercise groups; however, the magnitude of improvements was greater in the INT group. Only the INT group experienced reductions in erythrocyte malondialdehyde and serum von Willebrand factor and increases in plasma glutathione peroxidase and nitric oxide (all P < 0.05). We concluded that both continuous and interval training were effective in improving glycemic control, aerobic fitness, and endothelium-dependent vasodilation, but the interval training program appears to confer greater improvements than the continuous training program.

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Background-Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. Methods and Results-The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A 1c , hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0. 1-4 Hyperglycemia and hypertension are major risk factors for the development of microvascular disease.2,4 Intensive control of blood glucose and blood pressure to, or even beyond, currently recommended targets may provide some additional benefits in the prevention of diabetic microvascular disease but is often impossible to achieve because of the associated risks of hypoglycemia or hypotension. 5,6 Therefore, it is necessary to identify other targets and treatments to make progress in slowing the development of diabetic kidney disease and retinopathy. Clinical Perspective on p 1008Most epidemiological studies have found an association between serum triglycerides and diabetic kidney disease, although less consistently for serum high-density lipoprotein cholesterol (HDL-C). [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Results diverged among studies on diabetic retinopathy, especially in multivariable analysis. 4,[22][23][24][25][26][27][28][29][30][31][32][33] In randomized, controlled trials, treatment of patients with type 2 diabetes mellitus with fenofibrate, a peroxisome proliferatoractivated receptor-α agonist, reduced the rate of decline in renal function, 25,34 reduced albuminuria, and reduced the requirement for laser treatment of retinopathy. 5,25,34,35 However, it is not clear whether these beneficial effects were caused by improvements in triglycerides or HDL-C or by other biological effects of peroxisome proliferator-activated receptor-α activation.The objective of the present international study was to determine whether low HDL-C or elevated triglycerides levels are associated with diabetic kidney disease and retinopathy independent of established determinants of microvascular disease in patients with type 2 diabetes mellitus with low-density lipoprotein cholesterol (LDL-C) ≤3.4 mmol/L (130 mg/dL). MethodsThe study used a case-control desi...

Aims/hypothesis Maternal type 2 diabetes during pregnancy and gestational diabetes are associated with childhood adiposity; however, associations of lower maternal glucose levels during pregnancy with childhood adiposity, independent of maternal BMI, remain less clear. The objective was to examine associations of maternal glucose levels during pregnancy with childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. Methods The HAPO Study was an observational epidemiological international multi-ethnic investigation that established strong associations of glucose levels during pregnancy with multiple adverse perinatal outcomes. The HAPO Follow-up Study (HAPO FUS) included 4832 children from ten HAPO centres whose mothers had a 75 g OGTT at~28 weeks gestation 10-14 years earlier, with glucose values blinded to participants and clinical caregivers. The primary outcome was child adiposity, including:(1) being overweight/obese according to sex-and age-specific cut-offs based on the International Obesity Task Force (IOTF) criteria; (2) IOTF-defined obesity only; and (3) measurements >85th percentile for sum of skinfolds, waist circumference and per cent body fat. Primary predictors were maternal OGTT and HbA 1c values during pregnancy. Results Fully adjusted models that included maternal BMI at pregnancy OGTT indicated positive associations between maternal glucose predictors and child adiposity outcomes. For one SD difference in pregnancy glucose and HbA 1c measures, ORs for each child adiposity outcome were in the range of 1.05-1.16 for maternal fasting glucose, 1.11-1.19 for 1 h glucose, 1.09-1.21 for 2 h glucose and 1.12-1.21 for HbA 1c . Associations were significant, except for associations of maternal fasting glucose with offspring being overweight/obese or having waist circumference >85th percentile. Linearity was confirmed in all adjusted models. Exploratory sex-specific analyses indicated generally consistent associations for boys and girls. Conclusions/interpretation Exposure to higher levels of glucose in utero is independently associated with childhood adiposity, including being overweight/obese, obesity, skinfold thickness, per cent body fat and waist circumference. Glucose levels less than those diagnostic of diabetes are associated with greater childhood adiposity; this may have implications for long-term metabolic health.

The results of the present study indicate that the periodontal condition of older Thais with uncontrolled diabetes is: (a) significantly improved 3 months after mechanical periodontal therapy with adjunctive systemic antimicrobial treatment, and (b) rapidly deteriorating without periodontal treatment. The effect of periodontal therapy on the glycemic control of older uncontrolled diabetics will require further studies that will have to include much larger sample sizes.