Relationship Between Fasting Plasma Insulin Level and Resistance to Insulin-Mediated Glucose Uptake in Normal and Diabetic Subjects

Background: Despite optimal treatment, type II diabetes mellitus remains associated with an increased risk for future cardiovascular events. We sought to determine the association between baseline fasting plasma insulin levels and major adverse cardiovascular outcomes in patients with type II diabetes mellitus and high-risk vascular disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial. Methods: We included all patients with type II diabetes mellitus who had a central laboratory measured fasting plasma insulin level drawn at baseline as part of the study protocol. Hazard ratios were generated for the risk of major adverse cardiovascular outcomes (composite of cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina and coronary revascularization) with increasing quartile of baseline fasting plasma insulin level. We then performed a multivariable regression adjusting for significant baseline characteristics. Results: Among 12,092 patients in ACCELERATE, 2042 patients with type II diabetes mellitus had a baseline fasting plasma insulin level drawn. Median follow-up was 28 months. The study population had a mean age of 66.6 years, 79.2% male and 96.2% had established coronary artery disease. During follow-up, major adverse cardiovascular outcomes occurred in 238 patients (11.6%); of these events, 177 were coronary revascularization (8.7%). We observed a statistically significant relationship between rates of revascularization and rising quartile of baseline fasting plasma insulin level which was not noted for the other individual components of major adverse cardiovascular outcomes. Patients with type II diabetes mellitus who underwent revascularization were noted to have significantly higher baseline fasting plasma insulin levels (27.7 vs 21.4 mU/L, p-value = 0.009) although baseline haemoglobin A1c (6.63% vs 6.55%), body mass index (31.5 vs 31.1 kg/m2) and medical therapy were otherwise similar to the group not undergoing revascularization. Following multivariable regression adjusting for significant characteristics including exposure to evacetrapib, the log of baseline fasting plasma insulin level was found to be an independent predictor for major adverse cardiovascular outcomes (hazard ratio = 1.36, 95% confidence interval = 1.09–1.69, p-value = 0.007); this was driven by need for future revascularization (hazard ratio = 1.56, 95% confidence interval = 1.21–2.00, p-value = 0.001). Conclusion: In a contemporary population of patients with type II diabetes mellitus and high-risk vascular disease on optimum medical therapy, baseline hyperinsulinaemia was an independent predictor for major adverse cardiovascular outcomes and need of future coronary revascularization. These results suggest a pathophysiological link between hyperinsulinaemia and progression of atherosclerotic vascular disease among diabetics.

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Relationships between fetal growth and maternal body mass indices, plasma glucose level, and plasma insulin level in Japanese women with mildly impaired glucose tolerance

Journal of Obstetrics and Gynaecology Research ◽

10.1111/j.1447-0756.2011.01611.x ◽

2011 ◽

Vol 37 (12) ◽

pp. 1797-1801 ◽

Cited By ~ 2

Author(s):

Mamoru Morikawa ◽

Kazutoshi Cho ◽

Takashi Yamada ◽

Takahiro Yamada ◽

Rina Shono ◽

...

Keyword(s):

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Body Mass ◽

Glucose Level ◽

Fetal Growth ◽

Plasma Glucose ◽

Plasma Insulin ◽

Plasma Glucose Level ◽

Insulin Level ◽

Plasma Insulin Level

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Relationships between fasting plasma insulin, anthropometrics, and metabolic parameters in a very old healthy population

Metabolism ◽

10.1016/s0026-0495(98)90236-0 ◽

1998 ◽

Vol 47 (5) ◽

pp. 535-540 ◽

Cited By ~ 14

Author(s):

M. Carantoni ◽

G. Zuliani ◽

S. Volpato ◽

E. Palmieri ◽

A. Mezzetti ◽

...

Keyword(s):

Plasma Insulin ◽

Metabolic Parameters ◽

Healthy Population ◽

Very Old ◽

Fasting Plasma ◽

Fasting Plasma Insulin

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Increased Fasting Plasma Insulin Concentrations are Associated with the Severity of Angiographic Coronary Artery Disease

Angiology ◽

10.1177/000331970505600302 ◽

2005 ◽

Vol 56 (3) ◽

pp. 249-251 ◽

Cited By ~ 4

Author(s):

Rishi Sukhija ◽

Wilbert S. Aronow ◽

Devraj Nayak ◽

Chul Ahn ◽

Melvin B. Weiss

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Plasma Insulin ◽

Fasting Plasma ◽

Fasting Plasma Insulin ◽

Artery Disease

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Effect of clonidine on plasma insulin level in mice. Polia pharmacol

Folia Pharmacologica Japonica ◽

10.1254/fpj.74.383 ◽

1978 ◽

Vol 74 (3) ◽

pp. 383-388

Author(s):

Hikaru OZAWA ◽

Masayoshi GOTO ◽

Michiko TAKAHASHI ◽

Toshio UEMATSU

Keyword(s):

Plasma Insulin ◽

Insulin Level ◽

Plasma Insulin Level

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Effect of insulin on uric acid excretion in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.1.e1 ◽

1995 ◽

Vol 268 (1) ◽

pp. E1-E5 ◽

Cited By ~ 37

Author(s):

A. Quinones Galvan ◽

A. Natali ◽

S. Baldi ◽

S. Frascerra ◽

G. Sanna ◽

...

Keyword(s):

Uric Acid ◽

Plasma Insulin ◽

Excretion Rate ◽

Fractional Excretion ◽

Urine Flow ◽

Insulin Resistant ◽

Fasting Plasma ◽

Frequent Finding ◽

Fasting Plasma Insulin ◽

Induced Changes

Although hyperuricemia is a frequent finding in insulin-resistant states, insulin's effect on renal uric acid (UA) handling is not known. In 20 healthy volunteers, diastolic blood pressure, body weight, and fasting plasma insulin were positively (and age was negatively) related to fasting plasma UA concentrations, together accounting for 53% of their variability. During an insulin clamp, urine flow was lower than during fasting conditions (1.01 +/- 0.12 vs. 1.56 +/- 0.32 ml/min, P = 0.04), whereas creatinine clearance was unchanged (129 +/- 7 and 131 +/- 9 ml/min, P = not significant). Hyperinsulinemia did not alter serum UA concentrations (303 +/- 13 vs. 304 +/- 12 microM) but caused a significant decrease in urinary UA excretion [whether expressed as absolute excretion rate (1.66 +/- 0.21 vs. 2.12 +/- 0.23 mumol/min, P = 0.03), clearance rate (5.6 +/- 0.8 vs. 7.3 +/- 0.8 ml/min, P = 0.03), or fractional excretion (4.48 +/- 0.80 ml/min vs. 6.06 +/- 0.64%, P < 0.03)]. Hyperinsulinemia was also associated with a 30% (P < 0.001) fall in urine Na excretion. Fractional UA excretion was related to Na fractional excretion under basal conditions (r = 0.59, P < 0.01) and during the insulin period (r = 0.53, P < 0.02). Furthermore, the insulin-induced changes in fractional UA and Na excretion correlated with one another (r = 0.66, P < 0.001). Physiological hyperinsulinemia acutely reduces urinary UA and Na excretion in a coupled fashion.

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