The relation of proinsulin and insulin to insulin sensitivity and acute insulin response in subjects with newly diagnosed Type II diabetes: the Insulin Resistance Atherosclerosis Study

Mykkänen, Leena; Zaccaro, Daniel; Hales, C. N.; Festa, Andreas; Sm, Haffner

doi:10.1007/s001250051271

Cited by 65 publications

(56 citation statements)

References 33 publications

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“…24 Plasma proinsulin has also been found to have stronger associations than insulin with hypertension, dyslipidemia, and impaired glucose tolerance. 25 Fasting proinsulin was found to be more strongly correlated to measurements of insulin resistance than to measurements of acute insulin response, similar to the pattern of fasting specific insulin, 26,27 whereas the fasting proinsulin to insulin ratio was proposed as a marker for insulin secretion. 27 Thus, rather than being directly associated with its cause, proinsulin may be a marker of an underlying metabolic disturbance predisposing to atherosclerosis.…”

Section: Discussionmentioning

confidence: 74%

“…25 Fasting proinsulin was found to be more strongly correlated to measurements of insulin resistance than to measurements of acute insulin response, similar to the pattern of fasting specific insulin, 26,27 whereas the fasting proinsulin to insulin ratio was proposed as a marker for insulin secretion. 27 Thus, rather than being directly associated with its cause, proinsulin may be a marker of an underlying metabolic disturbance predisposing to atherosclerosis. 7 In vitro, proinsulin increases the plasminogen activator inhibitor-1 (PAI-1) production, 28 and in humans, plasma proinsulin was directly associated with PAI-1 concentrations.…”

Section: Discussionmentioning

confidence: 74%

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Proinsulin Is an Independent Predictor of Coronary Heart Disease

et al. 2002

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Background-Some, but not all, studies have reported a relationship between plasma insulin and coronary heart disease (CHD). Conventional nonspecific insulin assays are also measuring various fractions of proinsulin-like molecules due to cross-reactivity. The long-term relationship between proinsulin-like molecules and CHD is largely unknown. For this reason, the longitudinal relationships between intact proinsulin, split proinsulin, specific insulin, immunoreactive insulin, and CHD, were studied in a population-based cohort of 50-year-old men (nϭ874), with a follow-up of 27 years. Methods and Results-Fasting proinsulin-like molecule and specific-insulin concentrations were measured in plasma (stored frozen since baseline 1970 to 1973) by specific 2-site immunometric assays. Immunoreactive insulin concentrations were determined at baseline. The associations between proinsulin-like molecules, specific insulin, immunoreactive insulin, and CHD mortality (International Classification of Diseases [9th revision] codes 410 to 414) were analyzed using Cox's proportional hazards regression and presented as hazard ratios (HRs) with their 95% confidence intervals (CIs) for a 1-SD increase in a predictor variable. In the univariate analysis, intact proinsulin (HR, 1.69; 95% CI, 1.41 to 2.01) was the strongest predictor of death from CHD. In the multivariate analysis, smoking (HR, 1.57; 95% CI, 1.03 to 2.38), intact proinsulin (HR, 1.47; 95% CI, 1.18 to 1.82), systolic blood pressure (HR, 1.38; 95% CI, 1.14 to 1.66), and LDL/HDL cholesterol ratio (HR, 1.31; 95% CI, 1.12 to 1.53) were independent predictors of CHD mortality (adjusted for body mass index, triglycerides, and fasting glucose), whereas specific insulin and immunoreactive insulin were not (HR, 1.12; 95% CI, 0.90 to 1.40). The increased risk was restricted to the upper third of the proinsulin distribution. Conclusion-Increased proinsulin concentrations predict death and morbidity caused by CHD over a period of 27 years, independent of other major cardiovascular risk factors.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 74%

Proinsulin Is an Independent Predictor of Coronary Heart Disease

et al. 2002

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“…It has been shown that exercise reduces the plasma concentrations of triglycerides and increases the concentrations of HDL cholesterol [11]. A change in proinsulin concentrations could reflect a change in insulin sensitivity [23,24]. Insulin sensitivity and glucose disposal are improved by exercise [11].…”

Section: Discussionmentioning

confidence: 99%

“…Physical activity was inversely associated with mortality from cardiovascular diseases (and all causes). The association was weakened when adjusted for insulin, proinsulin and split proinsulin, factors related with insulin resistance [23,24], indicating that these metabolic factors could mediate the higher risk of mortality among sedentary individuals.…”

Section: Discussionmentioning

confidence: 99%

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Changes in physical activity are associated with changes in metabolic cardiovascular risk factors

2001

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Several studies have shown a beneficial effect of physical activity and exercise on health. A higher degree of or an increase in physical activity or physical fitness is associated with a lower risk of mortality or incidence of cardiovascular diseases [1±8], independent of several cardiovascular risk factors including smoking, obesity, blood pressure, serum lipids, socioeconomic status and diabetes [3±5].Physical activity also has a beneficial effect on many cardiovascular risk factors [2]. A higher degree of physical activity has been associated with a lower incidence of Type-II (non-insulin-dependent) diabetes mellitus [9] and a lower degree of insulin resistance [10,11]. Fasting concentrations of (immunore- Diabetologia (2001) Abstract Aims/hypothesis. To investigate the effect of changes in physical activity on changes in metabolic cardiovascular risk factors and to investigate what factors affect the association between physical activity and cardiovascular mortality. Methods. Of the 1860 men who were 50 years of age and who were without pre-existing cardiovascular disease participating in a population-based study, 898 were re-examined 20 years later. Altogether 231 died from cardiovascular diseases during the followup (mean = 22.6 years). The examinations which the men underwent at 50 and 70 years of age included assessment of physical activity (self-reported at four alternative levels), anthropometry, measurements of fasting concentrations of glucose, specific insulin, proinsulin, split proinsulin and lipids. Results. During the 20 years, 31 % increased their amount of physical activity while 51 % continued the same amount of exercise. Increased physical activity was associated with significant changes in several important metabolic variables, including fasting glucose, proinsulin and HDL cholesterol, independent of body weight changes. The risk of cardiovascular disease for men performing moderate, regular and athletic physical activity was 25 % (p = 0.127), 34 % (p = 0.022) and 71 % (p = 0.009) lower, respectively, compared with sedentary men. The association was attenuated by adjustment for baseline measurements of insulin, proinsulin and split proinsulin. Additional adjustment for other cardiovascular risk factors did not further attenuate the association. Conclusion/interpretation. Increased leisure time physical activity between the ages of 50 and 70 years, in the absence of active intervention, is associated with improved glucose, insulin and lipid metabolism in men. The concentrations of insulin, proinsulin and split proinsulin could mediate much of the association between a sedentary lifestyle and increased risk of cardiovascular mortality. [Diabetologia (2001)

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Effect of increasing duration of diabetes mellitus type 2 on glycated hemoglobin and insulin sensitivity

Verma

Paneri

Badi

et al. 2006

Indian J Clin Biochem

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Non-insulin dependent diabetes mellitus (NIDDM) is the most rapidly growing chronic metabolic disorder in the world. With advancement in the age and duration of diabetes there is a gradual tendency for the level of blood sugar to rise along with a subsequent increase in the HbA1c as well as in the fasting insulin level. Whether this is an aging process or increased frequency of diabetes is still controversial. The correlation between glucose and insulin sensitivity is consistent with the idea that the degree of chronic hyperglycemia is a cause of excessive insulin resistance in type 2 diabetes, i.e. the insulin resistance which characterizes type 2 diabetes but not nondiabetic subjects matched for age, gender, family history and duration of diabetes. The study comprised a total of 76 subjects out of which 30 were normal, non-diabetic persons and the rest 46 were diabetics with different duration of time in years, after being diagnosed diabetic. Data was analyzed after dividing the subjects into four groups-Group 1 comprised of one year old diabetics, Group 2 was made up of those, who had diabetes, for the past 2-5 years, Group 3 included patients who were diabetic since more than 5 years and Group 4 included non-diabetics as the normal control group. The results obtained indicated that the HbA1c levels showed a significant increase with the duration of diabetes as well as the insulin level showed a significant correlation after adjustment for age, sex and duration of diabetes.

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The relation of proinsulin and insulin to insulin sensitivity and acute insulin response in subjects with newly diagnosed Type II diabetes: the Insulin Resistance Atherosclerosis Study

Cited by 65 publications

References 33 publications

Proinsulin Is an Independent Predictor of Coronary Heart Disease

Proinsulin Is an Independent Predictor of Coronary Heart Disease

Changes in physical activity are associated with changes in metabolic cardiovascular risk factors

Effect of increasing duration of diabetes mellitus type 2 on glycated hemoglobin and insulin sensitivity

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