Manage gestational and pregestational diabetes mellitus in pregnancy

In one line

Diabetes in pregnancy is a continuum from gestational diabetes (GDM) to pre-existing type 1/type 2 disease, and management turns on separating the two early, driving glucose to tight targets, and managing the predictable obstetric harms — congenital anomaly, macrosomia, stillbirth, neonatal hypoglycaemia — rather than the glucose number alone.

This chapter assumes the diagnostic and first-line groundwork in diabetes & glucose-tolerance basics and the hypertension-in-pregnancy groundwork; it concentrates on subtype mechanism, the judgement calls, the named regimens and where guidelines disagree. Prevention of the pre-eclampsia that travels with diabetes is in Pre-eclampsia screening and aspirin prophylaxis.

Aetiology and pathophysiology — why the subtypes behave differently

That pregnancy is diabetogenic is assumed (placental lactogen, cortisol and progesterone drive a roughly second-half insulin resistance). What matters is classifying the disease by mechanism and reading each subtype's distinct obstetric signature off that mechanism. Four phenotypes sit under "hyperglycaemia first detected in pregnancy" (HFDP) plus the two pregestational types, and they do not behave alike.

• Type 1 diabetes (autoimmune β-cell failure). Absolute insulinopenia, so the patient is ketosis-prone and the dominant non-obstetric emergency is DKA — which in pregnancy arrives faster, at lower glucose, and kills the fetus (see below). Glycaemic lability is the rule: the same placental anti-insulin hormones that raise requirements also magnify the swing, so these women have the widest glycaemic variability and the strongest case for CGM. The clinical consequence: anomaly risk tracks periconceptional HbA1c, and intrapartum/neonatal hypoglycaemia is most severe because tight third-trimester control is hardest to hold.
• Type 2 diabetes (insulin resistance + relative insulinopenia). Now the commonest pregestational type in the SA public sector, riding the obesity epidemic. The mechanism is insulin resistance, so these women are older, heavier, more often hypertensive and dyslipidaemic, and frequently already vasculopathic at booking despite a "milder"-sounding diagnosis. The trap is complacency: outcome data repeatedly show T2DM pregnancies do as badly or worse than T1DM for stillbirth and perinatal death, because the disease is under-recognised, often poorly controlled at conception, and managed less intensively. The mechanism drives the consequence: established vascular disease (nephropathy, retinopathy, ischaemic heart disease) is what drives superimposed pre-eclampsia, growth restriction and the stillbirth excess — not the glucose alone.
• Overt (pregestational) diabetes first detected in pregnancy. A booking fasting ≥7.0 mmol/L, 2-hour OGTT ≥11.1 mmol/L or HbA1c ≥6.5% is pre-existing disease unmasked, not GDM. Mechanistically it has been hyperglycaemic through organogenesis, so it carries the anomaly and retinopathy risk of pregestational disease and is managed as such — the single most important classification call to get right.
• Gestational diabetes — and its two mechanistic sub-phenotypes. GDM is not one thing. Physiologically it splits into a predominantly insulin-resistant phenotype (the obese, metabolic-syndrome woman — looks like early T2DM, the larger group) and a predominantly insulin-deficient/β-cell-dysfunction phenotype (leaner, impaired secretory reserve). This is not academic: the insulin-resistant subtype responds to metformin and lifestyle and carries the macrosomia/LGA and later-T2DM risk, whereas the insulin-deficient subtype reaches insulin sooner and behaves more like nascent autoimmune or MODY disease. Suspect MODY (especially glucokinase, GCK-MODY) in the lean woman with a strong autosomal-dominant family history and mild, stable fasting hyperglycaemia that barely moves on treatment — here aggressively insulinising an unaffected fetus can cause growth restriction, while an affected fetus is appropriately macrosomic; the management pivots on fetal genotype, inferred from serial growth.

Two mechanism→consequence links unify the obstetric harms. First, the timing of the insult selects the lesion. Periconceptional hyperglycaemia is teratogenic (neural tube, the near-pathognomonic caudal regression/sacral agenesis, and cardiac and renal anomalies) because it acts during organogenesis — which is exactly why GDM, arising after organogenesis, does not raise anomaly risk and overt diabetes does. Late hyperglycaemia instead drives fetal hyperinsulinaemia (the Pedersen hypothesis): maternal glucose crosses the placenta, the fetal pancreas hypertrophies, and fetal insulin acts as a growth factor → asymmetric macrosomia (shoulders and trunk, hence shoulder dystocia), organomegaly, polyhydramnios, delayed surfactant maturation (RDS at term), and the neonatal hypoglycaemia that follows when the maternal glucose supply is cut at delivery but the hyperplastic islets keep secreting. Second, the vasculopathic placenta does the opposite of macrosomia — in the woman with nephropathy or long-standing disease, micro-vascular placental insufficiency gives growth restriction, abnormal Dopplers and the stillbirth risk, so the same diagnosis can present as either a 4.5 kg baby or a growth-restricted one depending on the maternal vascular bed. Both possibilities have to be held in mind at once.

(The old White classification — lettered by age of onset, duration and end-organ disease — is no longer recommended by ACOG and you should not lead with it; the modern stratifier is presence and severity of vasculopathy, which predicts adverse outcome better than duration-based class.)

Assessment

The first discrimination is GDM versus overt (pregestational) diabetes first detected in pregnancy — a distinction the term "hyperglycaemia first detected in pregnancy" (HFDP) is meant to force. A fasting glucose ≥7.0 mmol/L, a 2-hour OGTT value ≥11.1 mmol/L or an HbA1c ≥6.5% at booking is overt diabetes, not GDM: it carries the anomaly and retinopathy risk of pre-existing disease and is managed as such.

• Who to screen, when. SA practice (SEMDSA, mirroring WHO 2013) is predominantly risk-factor-based selective screening rather than universal — a resource-driven divergence from IADPSG universal screening. High-risk women (prior GDM, prior macrosomia, obesity, first-degree family history, glycosuria, PMOS (previously PCOS) — see Polyendocrine metabolic ovarian syndrome (PMOS)) get a 75 g OGTT at booking; if normal, repeat at 24–28 weeks. The HAPO-derived IADPSG/WHO 2013 GDM thresholds are any one of: fasting ≥5.1, 1-hour ≥10.0, 2-hour ≥8.5 mmol/L. NICE NG3 deliberately uses a different two-point threshold (fasting ≥5.6 or 2-hour ≥7.8 mmol/L) — the two guideline sets disagree, and which net is used materially changes who is diagnosed. The diagnostic thresholds side by side — the same 75 g OGTT read against two different nets:

The lower IADPSG/WHO net (used in SA) diagnoses more women than NICE; the woman with fasting 5.3 and 2-hour 7.0 is GDM by SA/IADPSG (fasting ≥5.1) but not by NICE (fasting <5.6 and 2-hour <7.8) — which is exactly the "overdiagnosis in a resource-limited system" debate below. (Note the boundary: had her 2-hour been ≥7.8 — say 8.0 — NICE would also diagnose her on its 2-hour limb, so it is the fasting-driven, sub-7.8 case that creates the fork.)

• Pre-existing diabetes booking work-up. Baseline HbA1c (also dates anomaly risk), renal function with albumin:creatinine ratio, dilated retinal screening, BP and a careful drug review — stop ACE-inhibitors/ARBs, statins and any GLP-1 receptor agonist or SGLT2-inhibitor preconceptionally.
• Interpretation. HbA1c quantifies anomaly risk: it climbs steeply above ~6.5% and a periconceptional HbA1c >86 mmol/mol (10%) is the NICE threshold at which pregnancy is actively advised against until improved. Proteinuria or rising creatinine flags nephropathy, which predicts superimposed pre-eclampsia and growth restriction.

The advanced assessment — atypical presentations and the judgement calls

Beyond the GDM-versus-overt split, the discriminations that matter are these:

• The threshold disagreement is a real management fork. A woman with fasting 5.3 and 2-hour 7.0 mmol/L is GDM by IADPSG/WHO and SA practice (fasting ≥5.1) but not by NICE NG3 (her fasting is below 5.6 and her 2-hour below 7.8). The fork only exists in this sub-7.8 2-hour window — if the 2-hour reaches ≥7.8 (e.g. 8.0) NICE also diagnoses her on the 2-hour limb. You must be able to say which net you are using and why — and recognise that the lower IADPSG net diagnoses more women, most of whom have the milder insulin-resistant phenotype that responds to lifestyle, which is the substance of the "overdiagnosis in a resource-limited system" debate.
• HbA1c misleads in exactly the women you most want to assess. The expanded red-cell mass and shortened erythrocyte survival of pregnancy lower HbA1c independently of glycaemia, and iron-deficiency anaemia falsely raises it while haemolysis, recent transfusion and late pregnancy falsely lower it — all common in the SA antenatal population. So HbA1c is a good booking anomaly-risk index but a poor monitoring tool in the third trimester; track capillary/CGM glucose, not serial HbA1c, near term. In a woman with a haemoglobinopathy (also common locally), HbA1c may be uninterpretable on standard assays altogether.
• Read the booking HbA1c as a teratogenicity dosimeter. It does not just "flag risk" — anomaly rate rises roughly continuously with periconceptional HbA1c, so a value of, say, 9–10% in a newly-presenting woman mandates a detailed anomaly scan (including fetal echocardiography at ~20–22 weeks and specific interrogation of the spine/sacrum for caudal regression), not routine surveillance. Conversely a near-normal booking HbA1c in known diabetes is genuinely reassuring about organogenesis and you can say so.
• The vasculopath hides in plain sight. A T2DM woman with microalbuminuria, a creatinine at the upper-normal limit, or background retinopathy is a different pregnancy from the metabolically-similar woman without end-organ disease: she is the one who develops early superimposed pre-eclampsia and FGR. Stratify by vasculopathy, look for it actively (ACR, creatinine, dilated fundoscopy, BP), and let it — not the glucose — drive the intensity of fetal surveillance and the aspirin decision.
• Retinopathy can accelerate because you tighten control. Rapid normalisation of long-standing hyperglycaemia, superimposed on pregnancy's own retinal effects, can transiently worsen proliferative retinopathy — which is why dilated screening is repeated (and why you do not crash the HbA1c in a woman who presents late with very poor control and untreated proliferative disease without ophthalmology input).
• Subtle/atypical pictures that change the plan: unexpectedly falling insulin requirements in the third trimester (placental insufficiency — investigate, see red flags); recurrent unexplained hypoglycaemia in early pregnancy (the physiological first-trimester dip, but also new Addison's or pituitary disease if profound); a lean woman with mild, treatment-resistant fasting hyperglycaemia and a dominant family history (think GCK-MODY before escalating insulin); and the vomiting T1DM woman with near-normal glucose who is actually in euglycaemic DKA.