Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study with long-term follow-up
PubMed 1357346 · doi:10.1016/0140-6736(92)92814-v
What was done
Researchers evaluated 155 normoglycaemic offspring from 86 families in which both parents had type 2 diabetes, following them prospectively for 6 to 25 years. Using intravenous glucose tolerance tests and minimal model analysis, they measured baseline insulin sensitivity (SI), glucose effectiveness (insulin-independent glucose uptake rate, SG), and first- and second-phase beta-cell secretion to determine the earliest metabolic predictors of disease development.
What was found
Subjects who developed type 2 diabetes had significantly lower baseline SI (mean 3.2 [SD 2.4] vs 8.1 [6.7] 10(-3) l min-1 pmol-1 insulin; p < 0.0001) and lower SG (1.6 [0.9] vs 2.3 [1.2] 10(-2) min-1; p < 0.0001) more than 10 years before diagnosis compared to those remaining normoglycaemic. For participants with both SI and SG below the group median, the 25-year cumulative incidence of diabetes was 76% (95% CI 54–99%), whereas 0% of participants with both values above the median developed diabetes. First-phase insulin secretion was increased rather than decreased during the prediabetic phase, matching the degree of insulin resistance.
Why it matters
This study demonstrates that both insulin-dependent and insulin-independent glucose disposal defects occur more than a decade before diabetes onset, establishing peripheral glucose clearance defects as primary early determinants before beta-cell compensation fails.
Limits
The study is restricted to a high-risk genetic cohort (offspring of two diabetic parents), limiting generalizability to the broader population. The sample size is relatively small (n = 155), follow-up duration varied widely (6–25 years), and potential lifestyle or environmental confounders were not reported in the abstract.
Cited by
- supports Hyperinsulinemia can be present and detectable decades before a person develops clinical hyperglycemia.