Gestational diabetes mellitus testing in the COVID-19 pandemic: The problems with simplifying the diagnostic process.

BACKGROUND: Multiple professional bodies have temporarily revised recommendations for gestational diabetes mellitus (GDM) testing during the COVID-19 pandemic to reduce person-to-person contact. The current Australian temporary criteria advise that if the fasting glucose is ≤4.6 mmol/L, then no glucose tolerance test (GTT) is required. AIMS: The aim of this study is to examine the extent of underdiagnosis of GDM using a fasting glucose ≤4.6 mmol/L as a cut-off to determine that a GTT is not necessary. MATERIALS AND METHODS: De-identified data from pregnant women having a GTT test in the Illawarra area during a six-year period was used to determine the number of women with GDM and the proportion of positive cases that would be missed for different fasting glucose values. RESULTS: There were 16 522 results identified and GDM was diagnosed in 12.2%. The majority of women were more than 30 years of age (85.2%) and diagnosed at ≥20 weeks gestation (81.1%). Of those diagnosed with GDM, 29% had a fasting glucose of ≤4.6 mmol/L and would have been missed. CONCLUSIONS: Our results show that using a fasting glucose of 4.6 mmol/L or less would miss nearly a third of women who would otherwise be diagnosed with GDM.

Routine glucose assessment in the emergency department for detecting unrecognised diabetes: a cluster randomised trial.

OBJECTIVE: To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow-up plans. DESIGN, SETTING: Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 - 31 December 2012; outcomes follow-up to 31 March 2016. PARTICIPANTS: Patients aged 18 years or more admitted to hospital from EDs. INTERVENTION: Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA1c ) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more. MAIN OUTCOME MEASURE: New diagnoses of diabetes and documented follow-up plans for patients with admission blood glucose levels of 14 mmol/L or more. RESULTS: Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow-up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26%; adjusted odds ratio [aOR], 0.83; 95% CI 0.42-1.7; P = 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31%; control, 86/278, 31%; aOR, 1.51; 95% CI, 0.83-2.80; P = 0.18). 30-day re-admission (31% v 22%; aOR, 1.34; 95% CI, 0.86-2.09; P = 0.21) and post-hospital mortality rates (24% v 22%; aOR, 1.07; 95% CI, 0.74-1.55; P = 0.72) were also similar for patients in intervention and control hospitals. CONCLUSION: Glucose and HbA1c screening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.

Seasonality, temperature and pregnancy oral glucose tolerance test results in Australia.

BACKGROUND: The oral glucose-tolerance test (OGTT) is currently the standard method for diagnosis of gestational diabetes (GDM). We conducted a post hoc analysis using the Australian Hyperglycemia and Adverse Pregnancy Outcome (HAPO) data to determine seasonal variations in OGTT results, the consequent prevalence of GDM, and association with select perinatal parameters. METHOD: Women enrolled in the Australian HAPO study sites (Brisbane and Newcastle) from 2001 to 2006 were included if OGTT results between 24 to 32 weeks gestation were available (n = 2120). Fasting plasma glucose, 1-h plasma glucose, 2-h plasma glucose, HbA1c, HOMA-IR, and umbilical cord C-peptide and glucose values were categorized by season and correlated to monthly temperature records from the Australian Bureau of Meteorology for Brisbane and Newcastle. GDM was defined post hoc using the IADPSG/WHO criteria. RESULTS: Small but significant (p <  0.01 on ANOVA) elevations in fasting glucose (+ 0.12 mM), HbA1c (+ 0.09%), and HOMA-IR (+ 0.88 units) were observed during the winter months. Conversely, higher 1-h (+ 0.19 mM) and 2-h (+ 0.33 mM) post-load glucose values (both p <  0.01) were observed during the summer months. The correlations between fasting glucose, 1-h glucose, 2-h glucose, and HbA1c with average monthly temperatures confirmed this trend, with positive Pearson's correlations between 1-h and 2-h glucose with increasing average monthly temperatures, and negative correlations with fasting glucose and HbA1c. Further, umbilical cord C-peptide and glucose displayed negative Pearson's correlation with average monthly temperature, aligned with trends seen in the fasting plasma glucose. Overall prevalence of GDM did not display significant seasonal variations due to the opposing trends seen in the fasting versus 1-h and 2-h post-load values. CONCLUSION: A significant winter increase was observed for fasting plasma glucose, HbA1c, and HOMA-IR, which contrasted with changes in 1-h and 2-h post-load venous plasma glucose values. Interestingly, umbilical cord C-peptide and glucose displayed similar trends to that of the fasting plasma glucose. While overall prevalence of GDM did not vary significantly by seasons, this study illustrates that seasonality is indeed an additional factor when interpreting OGTT results for the diagnosis of GDM and provides new direction for future research into the seasonal adjustment of OGTT results.

A cautionary response to SMFM statement: pharmacological treatment of gestational diabetes.

Use of oral agents to treat gestational diabetes mellitus remains controversial. Recent recommendations from the Society for Maternal-Fetal Medicine assert that metformin may be a safe first-line alternative to insulin for gestational diabetes mellitus treatment and preferable to glyburide. However, several issues should give pause to the widespread adoption of metformin use during pregnancy. Fetal concentrations of metformin are equal to maternal, and metformin can inhibit growth, suppress mitochondrial respiration, have epigenetic modifications on gene expression, mimic fetal nutrient restriction, and alter postnatal gluconeogenic responses. Because both the placenta and fetus express metformin transporters and exhibit high mitochondrial activity, these properties raise important questions about developmental programming of metabolic disease in offspring. Animal studies have demonstrated that prenatal metformin exposure results in adverse long-term outcomes on body weight and metabolism. Two recent clinical randomized controlled trials in women with gestational diabetes mellitus or polycystic ovary syndrome provide evidence that metformin exposure in utero may produce a metabolic phenotype that increases childhood weight or obesity. These developmental programming effects challenge the conclusion that metformin is equivalent to insulin. Although the Society for Maternal-Fetal Medicine statement endorsed metformin over glyburide if oral agents are used, there are few studies directly comparing the 2 agents and it is not clear that metformin alone is superior to glyburide. Moreover, it should be noted that prior clinical studies have dosed glyburide in a manner inconsistent with its pharmacokinetic properties, resulting in poor glycemic control and high rates of maternal hypoglycemia. We concur with the American Diabetes Association and American Congress of Obstetricians and Gynecologists, which recommend insulin as the preferred agent, but we believe that it is premature to embrace metformin as equivalent to insulin or superior to glyburide. Due to the uncertainty of the long-term metabolic risks of either metformin or glyburide, we call for carefully controlled studies that optimize oral medication dosing according to their pharmacodynamic and pharmacokinetic properties in pregnancy, appropriately target medications based on individual patterns of hyperglycemia, and follow the offspring long-term for metabolic risk.

The prevalence of gestational diabetes mellitus: The accuracy of the NSW perinatal data collection based on a private hospital experience.

Past studies have shown that the prevalence of gestational diabetes mellitus (GDM) has been underestimated, and this can have major implications for healthcare planning. With the changes in diagnostic criteria for GDM, we wanted to assess the accuracy of the diagnosis in a private hospital setting. Using data from the hospital's obstetric database, medical records and a private pathology provider, we established the true prevalence of GDM and compared it with the NSW Perinatal Data Collection. The recorded prevalence of 6.8% was well below the real value of 15.0%.

Fasting target for hyperglycaemia in pregnancy.

Knowledge of the fasting plasma glucose of healthy women may assist in the setting of treatment targets for women with hyperglycaemia in pregnancy (HIP). This study examines the pregnancy glucose tolerance test results of 3344 women without HIP collected over a three-year period. The median fasting plasma glucose was 4.4 mmol/L with an interquartile range of 4.2-4.6 mmol/L and a 5th to 95th centile of 3.8-4.9 mmol/L. As the diagnostic fasting glucose level for HIP is ≥5.1 mmol/L, these data support a treatment target of ≤5.0 mmol/L.

The prevalence of hyperglycaemia in pregnancy in Australia.

BACKGROUND: The Australasian Diabetes in Pregnancy Society (ADIPS) has recently endorsed the World Health Organization (WHO) terminology and classification of hyperglycaemia in pregnancy. The prevalence is likely to increase, but no prospective data are available for a representative Australian population. AIMS: To determine the prevalence of hyperglycaemia in pregnancy (HIP) using results from both the public and private sectors in a population that has a similar ethnicity to the overall Australian population. MATERIAL AND METHODS: The results of all pregnancy oral glucose tolerance tests (POGTT) in the public sector and by a dominant private pathology provider in a major city have been prospectively collected for a three-year period and analysed using the ADIPS (WHO) criteria. RESULTS: The prevalence of hyperglycaemia in pregnancy (HIP) was 13.1% with diabetes mellitus in pregnancy (DIP) being 0.4% and gestational diabetes mellitus (GDM) being 12.7%. CONCLUSION: The new criteria will diagnose about one-third more women with GDM than the previous ADIPS criteria. This will have resource and health implications. Focussed local health economic data will be important.

Carbohydrates, glycemic index, and pregnancy outcomes in gestational diabetes.

This review critically evaluates the current evidence regarding the effect of the dietary glycemic index (GI) on pregnancy outcomes in gestational diabetes mellitus (GDM). Current evidence, although limited, consistently supports the advantages of, and has demonstrated no disadvantages of, a low-GI diet. We conclude that pregnant women with GDM are likely to benefit from following a low-GI meal pattern, with no significant side effects, and consideration of the GI should be given when formulating a diet for GDM. However, until larger scale intervention trials are completed, an exclusive low-GI diet should not replace the current recommended diets for GDM from relevant government and health agencies. Further studies that intervene at an earlier stage of pregnancy are required.

The impact of potential new diagnostic criteria on the prevalence of gestational diabetes mellitus in Australia.

OBJECTIVE: The International Association of Diabetes and Pregnancy Study Groups (IADPSG) has proposed new criteria for the diagnosis of gestational diabetes mellitus (GDM). The aim of this study was to compare the prevalence of GDM when IADPSG criteria were used with the prevalence when the current Australasian Diabetes in Pregnancy Society (ADIPS) criteria were used. DESIGN, SETTING AND PARTICIPANTS: This was a prospective study over a 6-month period, examining the results of all glucose tolerance tests (GTTs) conducted for the diagnosis of GDM in Wollongong, a city using the public and private sectors. MAIN OUTCOME MEASURES: The prevalence of GDM using the existing (ADIPS) and the proposed (IADPSG) criteria. RESULTS: There were 1275 evaluable GTTs (571 public and 704 private). Using the current ADIPS diagnostic criteria, the prevalence of GDM was 8.6% (public), 10.5% (private) and 9.6% (overall). Using the proposed IADPSG criteria, the prevalence of GDM was 9.1% (public), 16.2% (private) and 13.0% (overall). CONCLUSIONS: The proposed IADPSG criteria would increase the prevalence of GDM from 9.6% to 13.0% (P < 0.001). In our study in the Wollongong area, which has a population with a predominantly white background, this increase came mainly from older women attending a private pathology provider. Data from both the public and private sectors need to be included in any discussion on the change in prevalence of GDM.

The ADIPS Pilot National Diabetes in Pregnancy Benchmarking Programme.

BACKGROUND: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia. METHODS: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services. RESULTS: The audit included 10,144 pregnancies (gestational diabetes mellitus (GDM) = 8696; type 1 diabetes (T1D) = 435; type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8-57.3%), metformin alone in 18.8% (0.4-43.7%), and metformin and insulin in 10.1% (1.5-23.4%); when compared between sites, all p < 0.001. Birth was by elective caesarean in 12.1% (3.6-23.7%) or emergency caesarean in 9.5% (3.5-21.2%) (all p < 0.001). Preterm births (<37 weeks) ranged from 3.7% to 9.4% (p < 0.05), large for gestational age 10.3-26.7% (p < 0.001), admission to special care nursery 16.7-25.0% (p < 0.001), and neonatal hypoglycaemia (<2.6 mmol/L) 6.0-27.0% (p < 0.001). Many women with T1D and T2D had limited pregnancy planning including first trimester hyperglycaemia (HbA1c > 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively (p < 0.001). CONCLUSION: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy.

Achieving glycosylated hemoglobin targets using the combination of repaglinide and metformin in type 2 diabetes: a reanalysis of earlier data in terms of current targets.

BACKGROUND: For patients with type 2 diabetes, the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) currently recommend a glycosylated hemoglobin (HbA(1c) ) target of <7%, and the British Medical Association (BMA) Quality and Outcomes Framework recommends an HbA(1c) target of >or=7.5%. OBJECTIVE: This letter presents a reanalysis of data from a previous study of the effect on glycemic control of adding repaglinide to metformin monotherapy in patients with type 2 diabetes to determine the proportion of patients achieving current ADA/EASD and BMA targets. METHODS: PubMed was searched using the terms repaglinide AND metformin AND HbA(1c) to identify published comparisons of monotherapy and combination therapy with these drugs in patients with type 2 diabetes. RESULTS: In the original analysis, which employed an HbA(1c) target of <7.1%, 59%of patients treated with metformin plus repaglinide achieved their glycemic target, compared with approximately 20% of patients treated with metformin or repaglinide alone. On reanalysis of the data according to the current ADA/EASD HbA(1c) target of <7%, 56% of patients receiving metformin and repaglinide achieved that goal,compared with 19%each in the groups treated with metformin or repaglinide monotherapy. On reanalysis of the data according to the BMA Quality and Outcomes Framework HbA(1c) target of >or=7.5%, 89% of patients receiving metformin and repaglinide achieved that goal, compared with 43%and 42% of patients receiving metformin and repaglinide monotherapy, respectively. CONCLUSION: Based on this reanalysis of earlier data in terms of currently recommended HbA(1c) targets, combination therapy with repaglinide and metformin would appear to be a good treatment option for patients with type 2 diabetes.

Mealtime 50/50 basal + prandial insulin analogue mixture with a basal insulin analogue, both plus metformin, in the achievement of target HbA1c and pre- and postprandial blood glucose levels in patients with type 2 diabetes: a multinational, 24-week, randomized, open-label, parallel-group comparison.

BACKGROUND: In people without diabetes, approximately 50% of daily insulin secretion is basal and the remainder is postprandial. Hence, it would be expected that insulin replacement therapy in a 50/50 ratio with each meal would mimic physiologic insulin secretion better than treatment with once-daily basal insulin in patients with diabetes mellitus. Using lispro mix (LM) 50/50 before meals may be a logical approach to achieving glycemic targets (glycosylated hemoglobin [HbA(lc)] and pre- and postprandial blood glucose [BG] concentrations) in these patients. OBJECTIVE: The aim of this study was to test the hypothesis that treatment with a premixed insulin analogue containing 50/50 basal + prandial insulins administered before each meal would achieve lower overall and mealtime glycemic control than once-daily basal insulin analogue, both plus metformin (Met), in patients with type 2 diabetes mellitus. METHODS: This 24-week, randomized, open-label, parallel-group trial was conducted at 38 sites across Australia, Greece, India, The Netherlands, Poland, Puerto Rico, and the United States. Male and female patients aged 35 to 75 years with type 2 diabetes mellitus and an HbA(1c) level of 6.5% to 11.0%, who were receiving metformin and/or a sulfonylurea with a stable dose of 0 to 2 daily insulin injections over the previous 3 months were eligible. Patients were randomly assigned to receive LM50/50 (50% insulin lispro protamine suspension [ILPS] and 50% lispro) TID plus metformin (to a maximally tolerated daily dosage of 500-1000 mg BID) (LM50/50 + Met) or insulin glargine QD at bedtime plus metformin (500-1000 mg BID) (G + Met) for 24 weeks. With LM50/50 + Met, the insulin dose was titrated to target a fasting BG (FBG) level of <6.7 mmol/L (<120 mg/dL) and a 2-hour post-prandial BG (PPBG) level of <8.0 mmol/L (<144 mg/dL); those who did not reach the FBG target would be switched from presupper LM50/50 to LM75/25 (75% ILPS, 25% lispro). RESULTS: A total of 315 patients were randomized and received treatment (158 women, 157 men; mean age, 57.7 years; mean body mass index, 32.1 kg/m2; LM50/50 + Met, 157 patients; G + Met, 158 patients). At 24 weeks, the mean (SD)HbA(1c) level was significantly lower in the LM50/50 + Met group than in the G + Met group (7.1% [0.9%] vs 7.5% [1.0%]; P<0.001), and the proportion who reached an HbA(1c) target of < or = 7.0% was greater (88 [56.1%] vs 63 [39.9%]; P = 0.005). The G + Met group had a lower mean (SD)FBG value (6.5 [1.6] vs 8.1 [1.8] mmol/L; P<0.001). The LM50/50 + Met group had lower mean preprandial BG levels prelunch (7.4 [1.9] vs 7.9 [2.1] mmol/L; P=0.03) and presupper (8.3 [2.0] vs 8.9 [2.8] mmol/L; P=0.04). The LM50/50 + Met group also had lower mean 2-hour PPBG values postbreakfast (8.7 [2.2] vs 9.2 [2.5] mmol/L; P=0.03), postlunch (8.4 [1.9] vs 9.8 [2.6], mmol/L; p<0.001), and postsupper (8.7 [2.2] vs 10.7 [3.2], mmol/L; P<0.001). The mean (SD) total insulin doses at study end point were 0.7 (0.3) U/kg in the LM50/50 + Met group and 0.6 (0.3) U/kg in the G + Met group (P<0.001). The mean (SD)M-value (an expression of mean glycemia and the effect of glucose swings) was statistically similar between the 2 groups at baseline but significantly lower in the LM50/50 + Met group at end point (17.3 [13.8] vs 25.1 [24.8] mmol/L; P<0.001). During the entire treatment period, mean (SD) overall and nocturnal hypoglycemia rates (episodes per patient for 30 days) were statistically similar between the 2 groups (overall, 0.8 [1.4] vs 0.5 [1.0]; nocturnal, 0.2 [0.7] vs 0.3 [0.6]). At end point, the mean (SD) nocturnal hypoglycemia rates were similar between the 2 groups (0.2 [0.9] vs 0.2 [0.6]), but the overall and non-nocturnal hypoglycemia rates were higher with LM50/50 + Met (overall, 0.7 [1.7] vs 0.3 [0.8]; P=0.02; non-nocturnal, 0.5 [1.2] vs 0.1 [0.4]; P=0.002). CONCLUSION: In these patients with type 2 diabetes, mealtime LM50/50 + Met was associated with lower overall (HbA(1c)) and preprandial BG and PPBG levels (except for FBG), with similar nocturnal hypoglycemia and less glycemic variability, compared with G + Met.

Effect of a low-glycemic-index diet during pregnancy on obstetric outcomes.

BACKGROUND: Pregnancy is a condition in which the glycemic index (GI) may be of particular relevance because maternal glucose is the main energy substrate for intrauterine growth. OBJECTIVE: The aim was to compare the effects of low-GI and conventional dietary strategies on pregnancy outcomes in healthy women. Compliance and acceptability were also investigated. DESIGN: The subjects were assigned alternately to receive dietary counseling that encouraged either low-GI (LGI) carbohydrate foods or high-fiber, moderate-to-high GI (HGI) foods and were studied 5 times between <16 wk gestation and delivery. Of the 70 women who met the inclusion criteria, 62 completed the study (32 in the LGI and 30 in the HGI groups). Primary outcomes were measures of fetal size. RESULTS: The mean diet GI fell significantly in the LGI group but not in the HGI group. Compared with the LGI group, women in the HGI group gave birth to infants who were heavier (3408 +/- 78 compared with 3644 +/- 90 g; P = 0.051) and had a higher birth centile (48 +/- 5 compared with 69 +/- 5; P = 0.005), a higher ponderal index (2.62 +/- 0.04 compared with 2.74 +/- 0.04; P = 0.03), and a higher prevalence of large-for-gestational age (3.1% compared with 33.3%; P = 0.01). Women in the LGI group found the diet easier to follow. CONCLUSION: Because birth weight and ponderal index may predict chronic disease in later life, a low-GI diet may favorably influence long-term outcomes.

Seasonal Changes in the Prevalence of Gestational Diabetes Mellitus.

OBJECTIVE: To determine the effect of different seasons on the prevalence of gestational diabetes mellitus (GDM) by using World Health Organization criteria. RESEARCH DESIGN AND METHODS: The results of all pregnancy glucose tolerance tests (GTTs) were prospectively collected over a 3-year period in a temperate climate, and the results were grouped by season. RESULTS: The results of 7,369 pregnancy GTTs were available for consideration. In winter, the median 1-h and 2-h glucose results after GTT were significantly (P < 0.0001) lower than the overall 1-h and 2-h results. The prevalence of GDM at the 1-h diagnostic level was 29% higher in summer and 27% lower in winter than the overall prevalence (P = 0.02). The prevalence of GDM at the 2-h diagnostic level was 28% higher in summer and 31% lower in winter than the overall prevalence (P = 0.01). CONCLUSIONS: The prevalence of GDM varies according to seasons, which leads to the possible overdiagnosis of GDM in summer and/or underdiagnosis in winter. Further research into standardization of the GTT or seasonal adjustment of the results may need to be considered.

A randomized clinical trial evaluating the safety and efficacy of sitagliptin added to the combination of sulfonylurea and metformin in patients with type 2 diabetes mellitus and inadequate glycemic control.

BACKGROUND: Type 2 diabetes mellitus (T2DM) treatment generally requires multiple antihyperglycemic agents. When diet, exercise, and treatment with sulfonylurea and metformin do not achieve glycemic goals, several options are available. The present study evaluated the efficacy and tolerability of sitagliptin 100 mg/day added to therapy with sulfonylurea and metformin. METHODS: Patients with HbA1c ≥7.5% and ≤10.5% while on a sulfonylurea and metformin were randomized 1: 1 to sitagliptin 100 mg/day or placebo for 24 weeks. At Week 24, patients in the placebo group switched to pioglitazone 30 mg/day and both groups continued treatment for another 30 weeks. RESULTS: Of 427 patients randomized, 339 (79.4%) completed the study. At Week 24, significantly greater (P < 0.001) mean reductions from baseline were seen in the sitagliptin versus placebo group for HbA1c (-0.84% vs -0.16%, respectively), 2-h post-meal glucose (-2.0 vs -0.2 mmol/L, respectively) and fasting plasma glucose (-0.7 vs 0.3 mmol/L, respectively). At Week 54, improvements in glycemic control continued. At Week 24, the incidence of adverse events (AEs) was numerically greater with sitagliptin than placebo, primarily because of a higher incidence of hypoglycemia. At Week 54, the incidence of AEs was similar in both groups, primarily because of a higher incidence of hypoglycemia and edema in the placebo/pioglitazone group after Week 24. The only meaningful change in body weight was an increase in the placebo/pioglitazone group at Week 54. CONCLUSIONS: In this study, sitagliptin 100 mg/day was generally well tolerated and provided improvement in glycemic control when added to the combination of sulfonylurea and metformin in patients with T2DM.