Sensitive and specific two-site immunoradiometric assays for human insulin, proinsulin, 65-66 split and 32-33 split proinsulins

Aims/hypothesis: We examined whether associations between low birthweight and adult chronic cardiometabolic disease were dependent upon birthweight alone, or on interactions with BMI, fat accumulation either generally or abdominally, or attained height in young South African adults. Methods: Blood pressure (BP), lipids, glucose tolerance, insulin sensitivity and secretion (homeostasis model) were measured in 20-year-olds (n=132) born at full term and with birthweights on or below the tenth centile (underweight for gestational age [UFA]) or between the 25th and 75th centiles for gestational age (appropriate weight for gestational age, [AFA]). Sex-specific median measurements of BMI, waist circumference, percentage body fat and height defined current anthropometric status, providing four groups for each measure: UFA-low or UFAhigh and AFA-low or AFA-high. Results: The UFA-high BMI group was more insulin-resistant than both low BMI groups (p<0.04), but not the AFA-high BMI group. In contrast, plasma triglycerides and systolic BP were higher in the UFA-high than in all other groups (all p<0.04). When characterised by body fatness, both high percentage (%) body fat groups had higher fasting [insulin] than low percentage (%) body fat groups (p<0.03), and higher [total cholesterol] and [LDL cholesterol] than the UFA-low percentage (%) body fat group (p<0.05). The UFA-high group had higher systolic and diastolic BP than all other groups (all at least p<0.03). A similar pattern was observed when groups were characterised by waist circumference; however, current height status had no effect. Conclusions/ interpretation: These data indicate that the "fetal origins" expression of the chronic disease phenotype is not dependent on birthweight alone, but on its interaction with subsequent fat accumulation, though not on attained height, in this cohort of young adults.

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“…Serum insulin, pro-insulin and split pro-insulin were measured by specific immunometric assays in Cambridge, UK [30].…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

Adult BMI and fat distribution but not height amplify the effect of low birthweight on insulin resistance and increased blood pressure in 20-year-old South Africans

et al. 2005

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“…Intact insulin, proinsulin and 32-33 split proinsulin were measured by in-house immunofluorimetric two-site assays (DELFIA system) based on published methods [9]. Inter-assay imprecision ranged from 6 to 10% (CV%) for low, medium and high-quality control samples for intact insulin, and from 7 to 15% for insulin precursors.…”

Section: Methodsmentioning

confidence: 99%

Type 2 diabetes mellitus is associated with increased axial bone density in men and women from the Hertfordshire Cohort Study: evidence for an indirect effect of insulin resistance?

et al. 2004

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Aims/hypothesis. Previous studies have suggested that the high bone density often observed in type 2 diabetic patients may be explained by insulin resistance. We explored this hypothesis in the Hertfordshire Cohort Study. Methods. A total of 465 men and 444 women aged 59 to 71 years and with no prior diagnosis of diabetes attended a clinic where a glucose tolerance test was performed and bone density measured at the femoral neck and lumbar spine. Biochemical markers of bone turnover (serum osteocalcin and urinary mean c-terminal cross-linking telopeptide of type II collagen) were measured in 163 men. Results. According to WHO criteria, 83 men and 134 women were diagnosed with impaired glucose tolerance and a further 33 men and 32 women were diagnosed as having type 2 diabetes. Bone density was higher in newly diagnosed diabetic subjects, with relationships stronger in women (p<0.001) than men (p<0.05) and attenuated by adjustment for body mass index. In both sexes, we observed positive correlations between the total femur and femoral neck bone mineral density with measures of insulin resistance (r=0.17-0.22), with stronger results observed in women. These relationships did not apply after adjustment for body mass index. Glucose status did not lead to differences in osteocalcin level or c-terminal cross-linking telopeptide of type II collagen levels. Conclusions/interpretation. Our findings suggest that hyperinsulinaemia may affect bone mineral density through indirect effects, e.g. body weight.Keywords Bone density · Diabetes · Insulin

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“…Fasting concentrations of intact proinsulin and 32 to 33 split proinsulin were analyzed using a 2-site immunometric assay technique, 18 and specific insulin by the Access Immunoassay System (Sanofi Pasteur Diagnostics). Because of a freezer failure, concentrations of intact and 32 to 33 split proinsulin and specific insulin were only analyzed in baseline plasma samples from 1306 subjects.…”

Section: Glucometabolic Variablesmentioning

confidence: 99%

Metabolic Risk Factors for Stroke and Transient Ischemic Attacks in Middle-Aged Men

Wiberg

Sundström

Ärnlöv

et al. 2006

Stroke

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Background and Purpose-The impact of lipometabolic and glucometabolic disturbances on stroke incidence remains to be characterized in detail. We investigated relations of a comprehensive panel of baseline lipometabolic and glucometabolic variables to incident fatal and nonfatal stroke or transient ischemic attack (TIA), and stroke subtypes. Methods-A community-based prospective study of 2313 middle-aged men invited to a health survey at age 50. Results-During a follow-up of up to 32 years, 421 developed stroke or TIA. In Cox proportional hazards analyses adjusting for treatment with cardiovascular drugs at baseline, 1-standard deviation increases in body mass index, systolic and diastolic blood pressures, serum proinsulin, and lipoprotein(a) were associated with 11 to 35% increased risk for subsequent stroke/TIA. Electrocardiographic left ventricular hypertrophy and smoking were also associated with a higher risk for stroke/TIA. Essentially the same variables were related to brain infarction/TIA. Higher proportions of palmitic (16:0), palmitoleic (16:1), and oleic acid (18:1) in cholesterol esters were associated with an increased risk, whereas a higher proportion of linoleic acid (18:2 n-6) was protective against stroke/TIA. Further adjusting all models also for hypertension, diabetes, the metabolic syndrome, serum cholesterol, atrial fibrillation, cardiovascular disease, smoking, and physical activity, essentially the same pattern was observed. Conclusions-Indices of an unhealthy dietary fat intake and a high serum lipoprotein (a) level predicted fatal and nonfatal stroke/TIA independently of established risk factors in a community-based sample of middle-aged men followed for 32 years. (Stroke. 2006;37:2898-2903.)

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Sensitive and specific two-site immunoradiometric assays for human insulin, proinsulin, 65-66 split and 32-33 split proinsulins

Cited by 342 publications

References 35 publications

Adult BMI and fat distribution but not height amplify the effect of low birthweight on insulin resistance and increased blood pressure in 20-year-old South Africans

Adult BMI and fat distribution but not height amplify the effect of low birthweight on insulin resistance and increased blood pressure in 20-year-old South Africans

Type 2 diabetes mellitus is associated with increased axial bone density in men and women from the Hertfordshire Cohort Study: evidence for an indirect effect of insulin resistance?

Metabolic Risk Factors for Stroke and Transient Ischemic Attacks in Middle-Aged Men

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