Trends in Plasma Insulin Among Healthy Adults May Have Role in Lipid, Lipoprotein Metabolism

Diabetes Rates Leveling Off in Adults
Diabetes Rates Leveling Off in Adults
A team of investigators assessed the impact of fasting and 2-hour insulin levels on risk of developing type 2 diabetes.

Among healthy, community-dwelling adults, fasting and 2-hour insulin levels were observed to have a potential role in lipid and lipoprotein metabolism, according to the results of a study published in BMJ Open Diabetes Research & Care.

Data for this study were sourced from the Framingham Heart Study. Individuals from the Offspring (n=4135) or Third-Generation (n=4095) cohorts who had undergone at least 1 examination during the 1991-1995, 1998-2001, 2002-2005, 2005-2008, 2008-2011, or 2011-2014 cycles were evaluated to identify trends in insulin and glucose levels. The healthy subsample was defined as nonsmokers who did not have prevalent diabetes, cardiovascular disease, dyslipidemia, hypertension, or abdominal obesity.

Overall, data were derived from 3295 men and 3977 women; mean age was 47±12 and 47±12 years, body mass index (BMI) was 27.9±4.3 and 26.2±5.6 kg/m2, 12% and 11% were receiving treatment for hypertension, median physical activity index was 35.3 (interquartile range [IQR], 32-40.7) and 34.2 (IQR, 31-38), and 17% and 17% were smokers, respectively.

Among men and women, respectively, median fasting plasma insulin level was 28 (IQR, 22-39) and 26 (IQR, 21-34) pmol/L, and mean fasting plasma glucose level was 97.0±8.5 and 91.9±8.9 mg/dL. A total of 841 men and 1299 women were determined to be healthy. The healthy cohort had a median fasting plasma insulin level of 25 (IQR, 19-35) and 23 (IQR, 18-30) pmol/L and a mean fasting plasma glucose level of 94.5±7.3 and 88.3±6.6 mg/dL among men and women, respectively.

After adjusting for fasting plasma glucose level and glycated hemoglobin (HbA1c), longitudinal correlates with fasting plasma insulin included male sex (b, -0.35; P <.0001), waist circumference (b, 0.31; P <.0001), triglycerides (b, 0.17; P <.0001), age (b, -0.10; P =.001), total-to-high-density lipoprotein cholesterol ratio (HDL-C; b, 0.11; P =.004), and systolic blood pressure (b, 0.07; P =.02).

For fasting plasma insulin level, after adjusting for fasting plasma glucose level and HbA1c, only triglycerides (b, 0.17; P =.004) were found to be significantly associated.

Two-hour plasma insulin level was associated with 2-hour plasma glucose level (b, 0.53; P <.0001), male sex (b, -0.50; P <.0001), log-fasting plasma insulin (b, 0.37; P <.0001), and total-to-HDL-C ratio (b, 0.12; P =.003) after accounting for fasting plasma insulin and glucose levels, as well as 2-hour glucose level.

Between 254 and 352 study participants were found to have new-onset type 2 diabetes at follow-up. Developing type 2 diabetes was associated with fasting plasma glucose level (adjusted hazard ratio [aHR], 2.76; 95% CI, 2.46-3.11; P <.0001), 2-hour glucose level (aHR, 1.91; 95% CI, 1.74-2.09; P <.0001), fasting plasma insulin level (aHR, 1.36; 95% CI, 1.21-1.52; P <.0001), 2-hour insulin level (aHR, 1.33; 95% CI, 1.23-1.44; P <.0001), and HbA1c (aHR, 1.27; 95% CI, 1.16-1.39; P <.0001).

This study may have been limited by the fact that insulin was measured using different methods across study cycles.

These data indicated that fasting and 2-hour insulin levels have both common and distinct clinical correlates, indicating relevance for glucose homeostasis and lipid metabolism. Additional research is needed to determine clinical cutoffs that may be a marker for future diabetes risk.


Lieb W, de Oliveira CM, Pan S, et al. Clinical correlates of plasma insulin levels over the life course and association with incident type 2 diabetes: the Framingham Heart Study. BMJ Open Diabetes Res Care. 2022;10(1):e002581. doi:10.1136/bmjdrc-2021-002581