Diabetes Across the Lifespan: Women, Older Adults, Pregnancy, and Athletes

How Common Is Diabetes, and Why Does Population Context Matter?

Diabetes is a mechanistically heterogeneous disease. Blood glucose is the shared metric, but the hormonal, physiological, and pharmacological context differs sharply by sex, age, reproductive status, and training load. Treating all patients with the same protocol generates avoidable harm.

The CDC estimates that 38.4 million Americans (11.6% of the population) have diabetes, and 97.6 million adults have prediabetes. 1 Type 1 diabetes (T1DM) accounts for roughly 5 to 10% of all cases, while type 2 diabetes (T2DM) makes up approximately 90 to 95%. 2 Each population subgroup described in this article operates under distinct pathophysiology, and guidelines now reflect that differentiation explicitly.

The American Diabetes Association (ADA) 2024 Standards of Medical Care in Diabetes state: "Diabetes management must be individualized based on patient preferences, comorbidities, and life context, with glycemic targets adjusted accordingly." 3

Individualizing care is not optional. The downstream cardiovascular, renal, and neonatal consequences of poorly matched treatment are well-documented and quantifiable.

Diabetes in Women: Sex-Specific Risks the Data Reveal

Women with T2DM carry a disproportionately higher cardiovascular burden than men with the same diagnosis. A 2014 meta-analysis published in Diabetologia pooling data from 64 cohorts (N=858,507) found that women with T2DM had a 27% greater excess relative risk of fatal cardiovascular disease compared with men with T2DM, after adjusting for shared risk factors. 4 The biological mechanisms include greater endothelial dysfunction per unit of hyperglycemia, more adverse lipid remodeling with hyperinsulinemia, and sex-hormone interactions with insulin signaling.

Women also show distinct pharmacokinetics for several glucose-lowering agents. Body composition differences (higher fat-to-lean ratio in women) alter the volume of distribution for metformin and some SGLT-2 inhibitors, which may require dose titration rather than automatic standard dosing. 5

Polycystic ovary syndrome (PCOS) creates a second pathway to insulin resistance in reproductive-age women. An estimated 50 to 80% of women with PCOS have insulin resistance regardless of body weight. 6 Metformin 1,500, 2 to 000 mg/day is guideline-endorsed for improving insulin sensitivity in PCOS and may reduce progression to overt T2DM. 7

After menopause, estrogen loss removes a protective effect on insulin sensitivity. Observational data show insulin resistance can increase by 15 to 20% within the first two years post-menopause, partly from central adiposity redistribution. 8 Hormone therapy in postmenopausal women with T2DM does not uniformly worsen glycemia; the KEEPS trial found that transdermal 17-beta estradiol 0.05 mg/day did not significantly raise fasting glucose over 48 months compared with placebo. 9

Sex-specific screening deserves separate emphasis. Women with a history of gestational diabetes have a 7-fold increased lifetime risk of T2DM compared with women whose pregnancies were normoglycemic. 10 Annual fasting glucose or HbA1c testing after a GDM pregnancy is not widely followed in practice but is explicitly recommended by ADA guidance.

Gestational Diabetes: Diagnosis, Targets, and Safe Treatment

Gestational diabetes mellitus (GDM) affects 5 to 9% of US pregnancies, with rates rising in parallel with obesity prevalence. 11 Uncontrolled GDM raises the risk of macrosomia, shoulder dystocia, neonatal hypoglycemia, cesarean delivery, and pre-eclampsia. For the mother, it accelerates risk of T2DM within 5 to 10 years after delivery.

Diagnosis follows one of two protocols: the two-step approach (50 g glucose challenge test, then 100 g oral glucose tolerance test if abnormal) or the one-step 75 g OGTT. The IADPSG one-step thresholds are fasting glucose ≥92 mg/dL, 1-hour ≥180 mg/dL, or 2-hour ≥153 mg/dL. 12

Glycemic targets in pregnancy (ADA 2024):

• Fasting: <95 mg/dL
• 1-hour postprandial: <140 mg/dL
• 2-hour postprandial: <120 mg/dL 3

Medical nutrition therapy (MNT) is the first-line intervention. A diet providing 175 g of carbohydrate per day distributed across three meals and two to three snacks, with an emphasis on low-glycemic-index sources, achieves target glucose in approximately 70 to 85% of GDM cases without medication. 13

When MNT alone fails, insulin is the preferred pharmacologic agent because it does not cross the placenta at therapeutic doses. NPH insulin at bedtime (starting dose 0.1, 0.2 units/kg) combined with rapid-acting insulin (lispro or aspart) before meals is standard practice. 14

Metformin and glyburide are sometimes used when insulin is refused or unavailable. The MiTy trial (N=502) showed that adding metformin to insulin in T2DM pregnancies reduced total insulin dose and gestational weight gain but was associated with a small increase in preterm birth that did not reach statistical significance. 15 Glyburide crosses the placenta and is associated with higher rates of neonatal hypoglycemia compared with insulin; its use has declined accordingly. 16

GLP-1 receptor agonists, including semaglutide (Ozempic, Wegovy) and liraglutide (Victoza), are contraindicated during pregnancy. Animal studies showed fetal growth restriction and skeletal abnormalities at supratherapeutic doses. 17 Women of reproductive age using semaglutide should discontinue the drug at least 2 months before attempting conception, given its half-life of approximately 1 week and the FDA-recommended washout period. SGLT-2 inhibitors (empagliflozin, dapagliflozin) are also contraindicated in the second and third trimesters due to fetal renal toxicity. 18

Post-partum follow-up is a critical gap. Only 30 to 50% of women with GDM complete a 6-to-12-week postpartum 75 g OGTT, despite its being standard of care. 19 A second test at 1 year and then every 1 to 3 years is recommended by the ADA for all women with prior GDM. 3

Diabetes in Older Adults: Avoiding the Twin Hazards of Over- and Under-Treatment

Older adults with diabetes face competing risks that make aggressive glycemic control potentially harmful. Hypoglycemia in a 78-year-old with reduced counter-regulatory response can trigger falls, fractures, and cardiac arrhythmias. At the same time, persistent hyperglycemia accelerates cognitive decline, increases infection risk, and worsens functional capacity.

The ADA 2024 Standards stratify HbA1c targets by functional status: 3

• Healthy older adults (minimal comorbidities, intact cognition): HbA1c <7.0 to 7.5%
• Complex/intermediate (multiple chronic conditions or mild cognitive impairment): HbA1c <8.0%
• Very complex/poor health (end-stage disease, moderate-to-severe dementia, 2+ ADL dependencies): HbA1c <8.5%, with avoidance of hypoglycemia as the primary goal

The ACCORD trial demonstrated the danger of over-treatment at the older end of the T2DM spectrum. Intensive glycemic control targeting HbA1c <6.0% increased all-cause mortality by 22% (hazard ratio 1.22 to 95% CI 1.01, 1.46, P=0.04) compared with standard therapy in high-cardiovascular-risk adults, a finding that ended the intensive arm early. 20

Sulfonylureas and insulin carry the highest hypoglycemia risk in older adults. When possible, GLP-1 receptor agonists or SGLT-2 inhibitors should replace them, given lower intrinsic hypoglycemia risk and cardiovascular or renal protection. The LEADER trial (N=9,340) showed liraglutide 1.8 mg/day reduced major adverse cardiovascular events (MACE) by 13% (HR 0.87 to 95% CI 0.78, 0.97) in T2DM adults with established cardiovascular disease or high risk. 21 A meaningful subset of LEADER participants were older than 60.

Renal function demands careful attention in older patients. Metformin should be dose-reduced when eGFR falls to 30 to 45 mL/min/1.73 m² and stopped below 30 mL/min/1.73 m². 22 SGLT-2 inhibitors lose both efficacy and safety margin below eGFR 45 mL/min/1.73 m² for most agents.

Sarcopenia compounds glucose dysregulation in this population. Skeletal muscle accounts for roughly 70 to 80% of insulin-stimulated glucose uptake; muscle loss directly worsens postprandial hyperglycemia independent of HbA1c. 23 Resistance exercise twice weekly is a non-pharmacologic intervention with strong evidence for improving insulin sensitivity and preserving muscle mass in older adults with T2DM. 24

Polypharmacy screening at every visit is essential. Corticosteroids, atypical antipsychotics, and some diuretics all raise glucose significantly, and older adults are disproportionately prescribed these agents. A review of medication lists using the Beers Criteria for potentially inappropriate prescribing should be standard practice. 25

Diabetes in Athletes: Exercise Physiology, Hypoglycemia Prevention, and Fueling Strategies

Exercise is a powerful glucose-lowering tool, but it also introduces acute hypoglycemia risk, particularly in insulin-treated athletes with T1DM. Understanding the direction and magnitude of glucose change during different exercise modalities allows for precise prevention.

Aerobic exercise (running, cycling, swimming at moderate intensity) typically lowers blood glucose by 1 to 2 mmol/L (18 to 36 mg/dL) per 30 minutes of activity. 26 Anaerobic or high-intensity interval exercise (HIIT) can paradoxically raise glucose acutely due to catecholamine-driven hepatic glucose output, though this is followed by a prolonged period of increased insulin sensitivity lasting 24 to 48 hours. 27

The 2017 consensus statement from Diabetes Care (representing the views of Exercise and Sports Science Australia and multiple T1DM research groups) recommends: 28

"Pre-exercise blood glucose targets of 7 to 10 mmol/L (126 to 180 mg/dL) for most aerobic exercise, with a higher target of 10 to 15 mmol/L (180 to 270 mg/dL) for intense or prolonged sessions lasting more than 60 minutes."

For insulin-treated athletes performing aerobic exercise, a 20 to 50% reduction in basal insulin dose before activity, or a temporary basal rate reduction of 50 to 80% starting 60 to 90 minutes before exercise on an insulin pump, can significantly reduce mid-exercise hypoglycemia. 28

Carbohydrate supplementation during exercise follows the same general sports nutrition guidance used in non-diabetic athletes but with tighter glucose monitoring. A rate of 30 to 60 g of fast-absorbing carbohydrate per hour of moderate sustained exercise (glucose or maltodextrin-based sports drinks or gels) is the standard recommendation. 29 For very high-intensity efforts exceeding 2.5 hours, up to 90 g/hour of mixed glucose-fructose can be absorbed without gastrointestinal distress.

Continuous glucose monitoring (CGM) has changed exercise management substantially. The FreeStyle Libre 3 and Dexcom G7 provide real-time glucose readings every 1 to 5 minutes, allowing athletes to track direction and rate of change rather than single-point values. A 2022 study in Diabetes Care (N=113 adults with T1DM) showed CGM use during exercise reduced time in hypoglycemia by 2.7 percentage points compared with self-monitored blood glucose alone. 30

Athletes with T2DM on non-insulin agents have considerably lower hypoglycemia risk during exercise. Metformin, SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists do not cause hypoglycemia as monotherapy. GLP-1 agents may actually improve exercise capacity; a 2023 RCT found semaglutide 1 mg/week improved VO2 peak by 4.2% over 16 weeks in obese T2DM adults, partly through reduced body weight and improved cardiac output. 31

The HealthRX Athlete-Diabetes Glucose Management Framework stratifies pre-exercise glucose targets, insulin adjustment protocols, and carbohydrate dosing by exercise type (aerobic vs. anaerobic), duration (<30 min, 30 to 60 min, >60 min), and diabetes treatment category (insulin-dependent T1DM, insulin-supplemented T2DM, non-insulin T2DM). This three-axis framework should be inserted as a clinical decision table during editorial review.

GLP-1 Receptor Agonists Across Special Populations: What the Trial Data Show

GLP-1 receptor agonists have become central to T2DM management over the past decade, but their use varies considerably across the populations discussed here.

In STEP-1 (N=1,961), semaglutide 2.4 mg weekly produced 14.9% mean body weight reduction at 68 weeks versus 2.4% for placebo (P<0.001), with secondary improvements in fasting glucose, HbA1c, blood pressure, and lipids. 32 Most participants had obesity with one or more cardiometabolic comorbidities, making the population broadly relevant to women and older adults with T2DM.

The SUSTAIN-6 trial (N=3,297) demonstrated that semaglutide 0.5 mg and 1 mg/week reduced MACE by 26% (HR 0.74 to 95% CI 0.58, 0.95, P<0.001 for non-inferiority) compared with placebo in T2DM patients with high cardiovascular risk. 33

For older adults specifically, a 2022 post-hoc analysis of SUSTAIN-6 found cardiovascular benefit was consistent across age subgroups, with no meaningful difference in safety events between participants older than 65 and younger participants. 34

In reproductive-age women, GLP-1 agents require contraceptive counseling. Gastrointestinal side effects may reduce oral contraceptive absorption. More significantly, unintended pregnancy on a GLP-1 agent requires immediate discontinuation and obstetric referral.

Monitoring Standards and When to Escalate Care

Effective monitoring is the infrastructure underlying all population-specific management.

HbA1c reflects average glucose over 8 to 12 weeks but has known limitations. In older adults with renal disease or hemoglobin variants, HbA1c may be artificially low or high, and fructosamine or time-in-range (TIR) from CGM should supplement it. 35 ADA 2024 defines optimal TIR as >70% of readings between 70 to 180 mg/dL (3.9 to 10.0 mmol/L) for most adults, with a modified target of >50% TIR for older or high-risk individuals. 3

Annual assessments should include: urine albumin-to-creatinine ratio (UACR), eGFR, dilated eye exam, foot exam with 10-g monofilament testing, and a fasting lipid panel. 36 Blood pressure target is <130/80 mmHg for most adults with T2DM per ADA and AHA guidelines. 37

Referral to endocrinology is appropriate when HbA1c remains above 9% despite three or more agents, when recurrent severe hypoglycemia occurs, when pregnancy is confirmed in a woman with pre-existing T1DM or T2DM, or when an insulin pump or CGM initiation is planned. 38