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  • 1
    Electronic Resource
    Electronic Resource
    New variants in the glycogen synthase gene (Gln71His, Met416Val) in patients with NIDDM from eastern Finland (1997)
    Springer
    Diabetologia 40 (1997), S. 1313-1319 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin resistance ; glycogen synthesis ; non-insulin-dependent diabetes mellitus ; heredity ; candidate gene.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Impaired glycogen synthesis after insulin stimulation accounts for most of the insulin resistance in patients with non-insulin-dependent diabetes mellitus (NIDDM). The glycogen synthase gene (GYS1), which encodes the rate-limiting enzyme for glycogen synthesis, is a promising candidate gene for NIDDM. Therefore, we screened all 16 exons of this gene by single-strand conformation polymorphism analysis in 40 patients with NIDDM (age 67 ± 2 years, body mass index 28.2 ± 0.6 kg/m2) from Taipalsaari, eastern Finland. The Gly464Ser variant (exon 11) and a silent polymorphism TTC342TTT (exon 7) have been reported previously. In addition, we found a new variant Gln71His (exon 2) and a new amino acid polymorphism Met416Val (exon 10). An additional sample of 65 patients with NIDDM and 82 normoglycaemic men (age 54 ± 1 years, body mass index 26.3 ± 1.4 kg/m2) were screened. The allele frequency of the TTC342TTT silent substitution was 0.29 in both NIDDM and normoglycaemic subjects. The Gln71His and Gly464Ser variants were found in 1 (1 %) and 3 (3 %) subjects, respectively, of the 105 NIDDM patients and in none of the 82 normoglycaemic men. The Met416Val polymorphism was found in 16 (15 %) of the 105 NIDDM patients and in 14 (17 %) of the 82 control subjects (all heterozygous). The Met416Val polymorphism was not associated with insulin resistance in two groups of normoglycaemic subjects. In conclusion, the new Gln71His and Met416Val substitutions and other variants of the glycogen synthase gene are unlikely to make a major contribution to insulin resistance and NIDDM in diabetic patients from eastern Finland. [Diabetologia (1997) 40: 1313–1319]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050826
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  • 2
    Electronic Resource
    Electronic Resource
    Total immunoreactive proinsulin, immunoreactive insulin and specific insulin in relation to conversion to NIDDM: the Mexico City Diabetes Study (1997)
    Springer
    Diabetologia 40 (1997), S. 830-837 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin ; proinsulin ; insulin secretion ; non-insulin-dependent diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Although insulin resistance and decreased insulin secretion are characteristic of established non-insulin-dependent diabetes mellitus (NIDDM), which of these metabolic abnormalities is the primary determinant of NIDDM is still controversial. A disproportionate increase in the proinsulin to insulin ratio has been proposed as a marker of compromised insulin secretion. We examined the association of fasting immunoreactive insulin (which cross-reacts with proinsulin), specific insulin (which does not cross-react with proinsulin), total immunoreactive proinsulin (or insulin precursors), and the fasting proinsulin/specific insulin ratio to the risk of developing NIDDM in the 3.25-year follow-up of the Mexico City Diabetes Study. These measurements were made in 85 subjects who subsequently converted to NIDDM (prediabetic subjects) and in 85 age and gender matched subjects who remained non-diabetic at follow-up (control subjects). Immunoreactive insulin, proinsulin and the proinsulin/specific insulin ratio were significantly higher in prediabetic than in control subjects. However, the relation between specific insulin and the development of NIDDM was weaker than for proinsulin or immunoreactive insulin. After further adjustment for obesity, body fat distribution and glucose tolerance status, proinsulin and the proinsulin/specific insulin ratio, but not specific or immunoreactive insulin, predicted conversion to NIDDM. A high proinsulin/specific insulin ratio predicted conversion to NIDDM both in subjects with normal and those with impaired glucose tolerance at baseline. We conclude that in prediabetic subjects increased proinsulin, a marker of islet cell distress or compromised insulin secretion, is associated with rapid conversion (within 3.25 years) to NIDDM even in obese populations. [Diabetologia (1997) 40: 830–837]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050756
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  • 3
    Electronic Resource
    Electronic Resource
    Serum proinsulin levels are disproportionately increased in elderly prediabetic subjects (1995)
    Springer
    Diabetologia 38 (1995), S. 1176-1182 
    Details
    ISSN: 1432-0428
    Keywords: Key words Proinsulin ; insulin ; insulin secretion ; non-insulin-dependent diabetes mellitus ; epidemiology ; follow-up study.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin resistance and impaired insulin secretion are thought to be the primary defects in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Disproportionately increased proinsulin relative to insulin levels are suggested to be an early indicator of a failing pancreas. We examined the relationship of fasting specific insulin, proinsulin, and 32, 33 split proinsulin concentrations, and the proinsulin: insulin ratio to the risk of developing NIDDM 3.5 years later in 65–74-year-old non-diabetic Finnish subjects participating in a population-based study (n = 892) on diabetes and heart disease. Altogether 69 subjects developed NIDDM over a 3.5-year follow-up (cases). The cases were compared to randomly-selected gender-matched control subjects (n = 69) and control subjects matched for gender, glucose tolerance status (normal or impaired), and body mass index (n = 69). There were no differences in insulin concentrations between cases and random or matched control subjects [median and interquartile range; 123 (77–154), 108 (74–143), 118 (83–145) pmol/l, p = 0.271]. Random control subjects had lower proinsulin and 32,33 split proinsulin concentrations and split proinsulin: insulin ratios compared to cases [5.7 (3.8–9.0) vs 7.3 (4.8–10.0) pmol/l, p = 0.005; 7.3 (4.5–13.0) vs 10.4 (7.1–18.0) pmol/l, p = 0.002; 0.073 (0.057–0.110) vs 0.097 (0.060–0.135), p = 0.003]. Matched control subjects had lower proinsulin concentrations and proinsulin: insulin ratios compared to cases [5.9 (4.0–7.7) vs 7.3 (4.8–10.0) pmol/l, p = 0.019; 0.048 (0.035–0.071) vs 0.064 (0.045–0.100), p = 0.008]. When cases were compared to matched control subjects a 1 SD increase in baseline proinsulin: insulin ratio was associated with a 1.37-fold risk (p = 0.020) of developing diabetes. Moreover, this association was independent of fasting glucose concentration at baseline. Thus, in elderly prediabetic subjects disproportionately increased proinsulin concentration, an indicator of defective insulin secretion, is associated with conversion to diabetes over a short time period. [Diabetologia (1995) 38: 1176–1182]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422366
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  • 4
    Electronic Resource
    Electronic Resource
    A preponderance of small dense LDL is associated with specific insulin, proinsulin and the components of the insulin resistance syndrome in non-diabetic subjects (1995)
    Springer
    Diabetologia 38 (1995), S. 1328-1336 
    Details
    ISSN: 1432-0428
    Keywords: Key words Insulin resistance syndrome ; low density lipoprotein size ; triglyceride ; high-density lipoprotein ; hypertension.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recently, the presence of small dense low density lipoprotein (LDL) has been postulated to be a stronger risk factor for coronary heart disease than large LDL. While small dense LDL has been associated with individual components of the insulin resistance syndrome such as hypertension, high triglyceride level, low high density (HDL) cholesterol, and diabetes mellitus, there has been little work exploring whether LDL size is decreased in subjects with multiple metabolic disorders. We examined the association of LDL size and pattern to specific insulin (which does not cross-react with proinsulin), proinsulin, increased triglyceride, decreased HDL, hypertension and impaired glucose tolerance in 488 non-diabetic subjects from the San Antonio Heart Study. LDL size was significantly related to specific insulin, proinsulin and the fasting proinsulin/insulin ratio. Small dense LDL was significantly associated with high triglyceride level, decreased HDL cholesterol, hypertension and impaired glucose tolerance. LDL size (Å) decreased in a stepwise fashion with increasing number of the metabolic disorders described above (zero 262.6 ± 9.4; one 257.0 ± 9.3; two 256.4 ± 9.4; three 249.0 ± 9.1; and four 244.9 ± 9.0). These results were similar in men and women and in non-Hispanic whites and Mexican Americans. The association between LDL size and the number of metabolic disorders remained statistically significant even after adjustment for obesity, body fat distribution, gender, ethnicity, proinsulin and insulin concentrations. Furthermore, decreases in LDL size are also significantly associated with both a selective beta-cell defect (as estimated by the fasting proinsulin/insulin ratio) and insulin resistance (as estimated by the fasting insulin concentrations) although the association was somewhat stronger for the latter. We conclude that small dense LDL may form part of the insulin resistance syndrome in non-diabetic subjects. [Diabetologia (1995) 38: 1328–1336]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401766
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  • 5
    Electronic Resource
    Electronic Resource
    Serum proinsulin levels are disproportionately increased in elderly prediabetic subjects (1995)
    Springer
    Diabetologia 38 (1995), S. 1176-1182 
    Details
    ISSN: 1432-0428
    Keywords: Proinsulin ; insulin ; insulin secretion ; non-insulin-dependent diabetes mellitus ; epidemiology ; follow-up study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin resistance and impaired insulin secretion are thought to be the primary defects in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Disproportionately increased proinsulin relative to insulin levels are suggested to be an early indicator of a failing pancreas. We examined the relationship of fasting specific insulin, proinsulin, and 32, 33 split proinsulin concentrations, and the proinsulin: insulin ratio to the risk of developing NIDDM 3.5 years later in 65–74-year-old non-diabetic Finnish subjects participating in a populationbased study (n=892) on diabetes and heart disease. Altogether 69 subjects developed NIDDM over a 3.5-year follow-up (cases). The cases were compared to randomly-selected gender-matched control subjects (n=69) and control subjects matched for gender, glucose tolerance status (normal or impaired), and body mass index (n=69). There were no differences in insulin concentrations between cases and random or matched control subjects [median and interquartile range; 123 (77–154), 108 (74–143), 118 (83–145) pmol/l, p=0.271]. Random control subjects had lower proinsulin and 32,33 split proinsulin concentrations and split proinsulin: insulin ratios compared to cases [5.7 (3.8–9.0) vs 7.3 (4.8–10.0) pmol/l, p=0.005; 7.3 (4.5–13.0) vs 10.4 (7.1–18.0) pmol/l, p=0.002; 0.073 (0.057–0.110) vs 0.097 (0.060–0.135), p=0.003]. Matched control subjects had lower proinsulin concentrations and proinsulin: insulin ratios compared to cases [5.9 (4.0–7.7) vs 7.3 (4.8–10.0) pmol/l, p=0.019; 0.048 (0.035–0.071) vs 0.064 (0.045–0.100), p=0.008]. When cases were compared to matched control subjects a 1 SD increase in baseline proinsulin: insulin ratio was associated with a 1.37-fold risk (p=0.020) of developing diabetes. Moreover, this association was independent of fasting glucose concentration at baseline. Thus, in elderly prediabetic subjects disproportionately increased proinsulin concentration, an indicator of defective insulin secretion, is associated with conversion to diabetes over a short time period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422366
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    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 (1999)
    Springer
    Diabetologia 42 (1999), S. 1060-1066 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Proinsulin ; insulin ; insulin secretion ; insulin resistance.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Proinsulin concentrations are increased relative to insulin concentrations in subjects with Type II (non-insulin-dependent) diabetes mellitus. This could be secondary to hyperglycaemia or insulin resistance or due to a defect in insulin secretion. Methods. We investigated the association between fasting insulin, intact proinsulin and the intact proinsulin: insulin ratio with insulin sensitivity, estimated by a frequently sampled intravenous glucose tolerance test and the minimal model and with acute insulin response (AIR) in 182 newly diagnosed Type II diabetic subjects aged 40 to 69 years. None of the subjects was receiving hypoglycaemic medication. Results. Insulin sensitivity correlated inversely with fasting insulin (r s = –0.42) and intact proinsulin (r s = –0.32) (p 〈 0.001). The intact proinsulin:insulin ratio was not correlated with insulin sensitivity. AIR correlated positively with intact proinsulin (r s = 0.23) and inversely with the intact proinsulin:insulin ratio (r s = –0.29, p 〈 0.001). Fasting glucose correlated positively with intact proinsulin (r s = 0.34) and the intact proinsulin:insulin ratio (r s = 0.24, p 〈 0.001). The intact proinsulin:insulin ratio increased by decreasing AIR (quartiles of AIR from high to low: 7.8, 8.2, 9.7 and 12.1 %, p 〈 0.001). This association was independent of age, sex, ethnicity, body mass index, fasting glucose, and insulin sensitivity. Conclusion/interpretation. Insulin resistance (low insulin sensitivity) was not related to the intact proinsulin:insulin ratio in subjects with Type II diabetes. In contrast, both low AIR and high fasting glucose concentrations were associated with a disproportionate increase in proinsulin concentration. These results suggest that increased intact proinsulin:insulin ratio is a marker of a defect in insulin secretion in Type II diabetic subjects. [Diabetologia (1999) 42: 1060–1066]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051271
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  • 7
    Electronic Resource
    Electronic Resource
    Is microalbuminuria part of the prediabetic state? The Mexico City Diabetes Study (1993)
    Springer
    Diabetologia 36 (1993), S. 1002-1006 
    Details
    ISSN: 1432-0428
    Keywords: Microalbuminuria ; Type 2 (non-insulin-dependent) diabetes mellitus ; dyslipidaemia ; blood pressure ; insulin resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Microalbuminuria is associated with increased cardiovascular mortality in both diabetic and non-diabetic subjects. A number of studies have indicated that insulin resistance, increased blood pressure and dyslipidaemia precede the onset of clinical diabetes. We examined various correlates of microalbuminuria in 1,298 non-diabetic subjects who participated in the Mexico city Diabetes Study, a population-based study of diabetes and cardiovascular risk factors. Both parental history of diabetes and impaired glucose tolerance were significantly associated with microalbuminuria. These results were not explained by differences in age or blood pressure between subjects with or without a parental history of diabetes or impaired glucose tolerance. In addition, subjects with microalbuminuria had increased 2-h insulin and triglyceride concentrations, a higher prevalence of hypertension, and decreased high density lipoprotein cholesterol concentrations relative to subjects without microalbuminuria. These results suggest that microalbuminuria may be a feature of the prediabetic state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02374491
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    Paper (German National Licenses)
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  • 8
    Electronic Resource
    Electronic Resource
    A preponderance of small dense LDL is associated with specific insulin, proinsulin and the components of the insulin resistance syndrome in non-diabetic subjects (1995)
    Springer
    Diabetologia 38 (1995), S. 1328-1336 
    Details
    ISSN: 1432-0428
    Keywords: Insulin resistance syndrome ; low density lipoprotein size ; triglyceride ; high-density lipoprotein ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recently, the presence of small dense low density lipoprotein (LDL) has been postulated to be a stronger risk factor for coronary heart disease than large LDL. While small dense LDL has been associated with individual components of the insulin resistance syndrome such as hypertension, high triglyceride level, low high density (HDL) cholesterol, and diabetess mellitus, there has been little work exploring whether LDL size is decreased in subjects with multiple metabolic disorders. We examined the association of LDL size and pattern to specific insulin (which does not cross-react with proinsulin), proinsulin, increased triglyceride, decreased HDL, hypertension and impaired glucose tolerance in 488 non-diabetic subjects from the San Antonio Heart Study. LDL size was significantly related to specific insulin, proinsulin and the fasting proinsulin/insulin ratio. Small dense LDL was significantly associated with high triglyceride level, decreased HDL cholesterol, hypertension and impaired glucose tolerance. LDL size (å) decreased in a stepwise fashion with increasing number of the metabolic disorders described above (zero 262.6±9.4; one 257.0±9.3; two 256.4±9.4; three 249.0±9.1; and four 244.9±9.0). These results were similar in men and women and in non-Hispanic whites and Mexican Americans. The association between LDL size and the number of metabolic disorders remained statistically significant even after adjustment for obesity, body fat distribution, gender, ethnicity, proinsulin and insulin concentrations. Furthermore, decreases in LDL size are also significantly associated with both a selective beta-cell defect (as estimated by the fasting proinsulin/insulin ratio) and insulin resistance (as estimated by the fasting insulin concentrations) although the association was some-what stronger for the latter. We conclude that small dense LDL may form part of the insulin resistance syndrome in non-diabetic subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401766
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Prevalence of diabetes mellitus in elderly subjects in east Finland (1987)
    Springer
    Diabetologia 30 (1987), S. 195-196 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00274231
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