Core mechanism
In HHS, the pancreas retains a small but clinically meaningful amount of endogenous insulin secretion. The metabolic pathways that produce ketones are far more sensitive to insulin than the pathways that move glucose into cells.
Suppression of lipolysis and hepatic ketogenesis requires much lower insulin concentrations than stimulation of peripheral glucose uptake. Therefore, in HHS the residual insulin is enough to restrain adipose tissue breakdown and keep ketone production low, but not enough to lower blood glucose effectively.
Why glucose climbs so high
Because insulin cannot drive glucose into muscle and adipose tissue normally, hyperglycemia worsens. At the same time, osmotic diuresis caused by glucosuria produces profound dehydration and a falling glomerular filtration rate.
Dehydration further reduces urinary glucose excretion, allowing glucose to accumulate to levels far higher than those typically seen in DKA. The result is marked hyperglycemia with hyperosmolality but only mild ketosis.
Comparison of DKA and HHS
| Feature | DKA | HHS |
|---|
| Residual insulin | Very low or absent | Small amount still present |
| Lipolysis and ketogenesis | Markedly activated | Partially suppressed |
| Ketone production | High | Low or mild |
| Glucose elevation | Usually 250–600 mg/dL | Often >600 mg/dL |
| Dehydration severity | Moderate | Profound |
| Acidosis | Present | Usually absent or mild |
Why the other options are incorrect
Option 1 is incorrect because glucagon is not suppressed in HHS. In fact, elevated glucagon contributes to ongoing hepatic glucose output and hyperglycemia. Option 2 is incorrect because ketones are not lost in urine at a rate that matches hepatic production; ketonuria reflects excess production, not a disposal mechanism that prevents ketosis. Option 3 is incorrect because dehydration does not divert hepatic metabolism toward lactate instead of ketones. The primary determinant of ketogenesis is the insulin-to-glucagon ratio, not hydration status.
Key point! HHS and DKA exist on a spectrum of relative insulin deficiency. The presence of even small amounts of insulin in HHS is sufficient to block ketogenesis but insufficient to control glucose, which is why hyperglycemia and hyperosmolality dominate the clinical picture.
Watch out! Do not assume that very high glucose always means severe ketosis; the degree of ketosis depends on how much insulin action remains.