Q.5How should blood glucose and ketones be monitored in the preconception period?

Bibliographic InformationStudy Type & Evidence LevelNumber of PatientsPatient CharacteristicsIntervention & ComparisonFollow-up & Outcome MeasuresEffect SizeStudy SummaryReviewer Comments
The Diabetes Control and Complications Research Group
1993

70
Study Type: RCT

Evidence level: 1++
711 intensive therapy
730 conventional therapy
Type 1 diabetes aged 13–39 years. Absence of hypertension, hypercholesterolemia and severe diabetic complications or medical conditions.

Country: US and Canada
Intervention: Intensive therapy (IT): Aimed at achieving preprandial blood glucose concentrations between 3.9 and 6.7 mmol/l, postprandial concentrations of <10 mmol/l, a weekly 3am measurement >3.6 mmol/l and HbA1c measured monthly within the normal range (<6.05%). Intensive therapy included the administration of insulin 3 or more times a day by injection or external pump. The dosage was adjusted according to the results of self monitoring of blood glucose performed at least four times per day, dietary intake and anticipated exercise.

Comparison:
Conventional therapy (CT). CT consisted of 1 or 2 daily injections of insulin, daily self-monitoring of urine or blood glucose, and education about diet or exercise.
Follow-up period:
mean 6.5 years

Outcome Measures: HbA1c
Progression of retinopathy: change of at least three steps from baseline that was sustained for at least six months (early treatment diabetic retinopathy Study scale).
Proliferative retinopathy Severe nonproliferative retinopathy

Secondary outcomes Nephropathic Neuropathic Neuropsychological Macrovascular Quality of life outcomes
A statistically significant difference in the average HbA1c was maintained after baseline between the IT and CT groups (P < 0.001).
The mean (SD) value for all glucose profiles in the IT group was 8.6 ±1.7 mmol/l vs. 12.8±3.1 mmol/l in the CT group (P < 0.0001).

Primary prevention cohort (i.e. no retinopathy at baseline, n = 348 IT, 378 CT):
Intensive therapy reduced the adjusted mean risk for developing retinopathy by 76% (95% CI 62–85%) as compared with conventional therapy.
Secondary intervention cohort:
Intensive therapy slowed the progression of retinopathy by 54% (95% CI 14–67%)

Intensive therapy reduced the occurrence of microalbuminuria by 39%, albuminuria by 54% and clinical neuropathy by 60%.

In the IT group there were 62 hypoglycaemic episodes requiring assistance per 100 patient years vs. 19 episodes per 100 patient years in the CT group (P < 0.001).There were two fatal motor vehicle accidents (1 from each group).

There was no difference in QOL between the two groups.

Early worsening:
There was a transient worsening of retinopathy with intensive therapy (22% in IT vs. 13% in CT). The abnormalities often disappeared by 18 months. Patients with early worsening who underwent intensive therapy had a 74% (95% CI 46–88%) reduction in the risk of subsequent progression as compared with patients with early worsening who received conventional therapy (P < 0.001).

Secondary analysis:
There was a continuously increasing risk of sustained progression by three steps with increasing mean HbA1c.
Intensive therapy with the goal of achieving blood glucose concentrations as close as possible to the nondiabetic range delays onset and slows the progression of long- term diabetic complications.
The Diabetes Control and Complications Trial Research Group;

1996 Apr

49
Study Type: Cohort

Evidence level: 2++
180 women completed 270 pregnancies. 94 women originally assigned to intensive treatment. 86 women originally assigned to conventional treatment (26 changed to intensive treatment before conception, 60 after conception).Type 1 diabetes, in good health.

Country: US and Canada
Intervention: Women originally assigned to intensive treatment

Goals for all pregnant women fasting level 3.85– 5.5 mmol/l, 1 hour postprandial level 7.7 mmol/l

Comparison: Women originally assigned to conventional treatment
Follow-up period: 9 months

Outcome Measures:
Spontaneous abortion congenital malformation

HbA1c
Intensive treatment group mean HbA1c at conception 7.4%±1.3%. Conventional treatment group mean HbA1c at conception 8.1%±1.7%, P = 0.0001.

Nine congenital malformations were identified, 8 in the conventional treatment group (P = 0.06).

There were 18 (13.3%) spontaneous abortions in the intensive group and 14 (10.4%) in the conventional group (NS).

Overall the median HbA1c level was higher in those women who had abnormal outcomes (ectopic pregnancy, spontaneous abortion, induced abortion for medical reasons, congenital malformations, intrauterine death, neonatal death) than in those women with normal outcomes (P = 0.05). At the 3 months prior to conception P = 0.018 and at 5 months P = 0.019.
Timely institution of intensive therapy is associated with rates of spontaneous abortion and congenital malformations similar to those in the nondiabetic population.

From: Evidence tables

Cover of Diabetes in Pregnancy
Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the Postnatal Period.
NICE Clinical Guidelines, No. 63.
National Collaborating Centre for Women's and Children's Health (UK).
London: RCOG Press; 2008 Mar.
Copyright © 2008, National Collaborating Centre for Women’s and Children’s Health.

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