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Hyperglycaemic siblings of Type II (non-insulin-dependent) diabetic patients have increased PAI-1, central obesity and insulin resistance compared with their paired normoglycaemic sibling.
Diabetologia. 2002 May; 45(5):635-41.D

Abstract

AIMS/HYPOTHESIS

First-degree relatives of Type II (non-insulin-dependent) diabetic patients in cross-sectional studies have increased insulin resistance, associated cardiovascular risk factors and abnormalities of fibrinolysis and coagulation. To minimise between-family genetic and environmental confounders, we investigated within-family relationships between early hyperglycaemia and risk factors.

METHODS

Thirteen age and gender matched sibling pairs of Type II (non-insulin-dependent) diabetic patients, one hyperglycaemic, one normoglycaemic (fasting plasma glucose at screening 6.0-7.7 mmol.l(-1) and < 6.0 mmol.l(-1), respectively) were assessed for plasminogen activator inhibitor antigen (PAI-1), tissue plasminogen activator antigen (t-PA), fibrinogen, Factor VII and Factor VIII/von Willebrand factor antigen. Fasting lipid profiles, blood pressure and HOMA insulin sensitivity (%S) were also measured in siblings and in matched subjects without family history of diabetes.

RESULTS

Hyperglycaemic and normoglycaemic siblings (7 female, 6 male) were aged, mean (SD) 56.8 (8.7) and 55.8 (8.4) years. Hyperglycaemic siblings had increased PAI-1 antigen, geometric mean (i.q.r.): 26.3 (15.1-45.6) vs 11.1 (2.1-23.3) ng/ml, p=0.0002, similar t-PA antigen, mean (SD) 9.5 (4.3) vs 7.4 (2.5) ng/ml, p=0.2 and fibrinogen 2.2 (0.3) vs 2.3 (0.6) g/l, p=0.5, and reduced %S 66.3 (30.5) vs 82.9 (25), p=0.04. PAI-1 correlated negatively with %S (r=-0.55, p=0.005). No significant differences were found in blood pressure or fasting lipids.

CONCLUSION/INTERPRETATION

A minor increase in plasma glucose in non-diabetic sibling pairs of Type II (non-insulin-dependent) diabetic patients was associated with reduced insulin sensitivity, increased central adiposity and a doubling of PAI-1 antigen concentration, suggesting impaired fibrinolysis. It is possible that this could contribute to increased cardiovascular risk in these subjects.

Authors+Show Affiliations

Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

12107743

Citation

Herlihy, O M., et al. "Hyperglycaemic Siblings of Type II (non-insulin-dependent) Diabetic Patients Have Increased PAI-1, Central Obesity and Insulin Resistance Compared With Their Paired Normoglycaemic Sibling." Diabetologia, vol. 45, no. 5, 2002, pp. 635-41.
Herlihy OM, Barrow BA, Grant PJ, et al. Hyperglycaemic siblings of Type II (non-insulin-dependent) diabetic patients have increased PAI-1, central obesity and insulin resistance compared with their paired normoglycaemic sibling. Diabetologia. 2002;45(5):635-41.
Herlihy, O. M., Barrow, B. A., Grant, P. J., & Levy, J. C. (2002). Hyperglycaemic siblings of Type II (non-insulin-dependent) diabetic patients have increased PAI-1, central obesity and insulin resistance compared with their paired normoglycaemic sibling. Diabetologia, 45(5), 635-41.
Herlihy OM, et al. Hyperglycaemic Siblings of Type II (non-insulin-dependent) Diabetic Patients Have Increased PAI-1, Central Obesity and Insulin Resistance Compared With Their Paired Normoglycaemic Sibling. Diabetologia. 2002;45(5):635-41. PubMed PMID: 12107743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hyperglycaemic siblings of Type II (non-insulin-dependent) diabetic patients have increased PAI-1, central obesity and insulin resistance compared with their paired normoglycaemic sibling. AU - Herlihy,O M, AU - Barrow,B A, AU - Grant,P J, AU - Levy,J C, Y1 - 2002/04/26/ PY - 2001/05/14/received PY - 2001/12/24/revised PY - 2002/7/11/pubmed PY - 2003/1/4/medline PY - 2002/7/11/entrez SP - 635 EP - 41 JF - Diabetologia JO - Diabetologia VL - 45 IS - 5 N2 - AIMS/HYPOTHESIS: First-degree relatives of Type II (non-insulin-dependent) diabetic patients in cross-sectional studies have increased insulin resistance, associated cardiovascular risk factors and abnormalities of fibrinolysis and coagulation. To minimise between-family genetic and environmental confounders, we investigated within-family relationships between early hyperglycaemia and risk factors. METHODS: Thirteen age and gender matched sibling pairs of Type II (non-insulin-dependent) diabetic patients, one hyperglycaemic, one normoglycaemic (fasting plasma glucose at screening 6.0-7.7 mmol.l(-1) and < 6.0 mmol.l(-1), respectively) were assessed for plasminogen activator inhibitor antigen (PAI-1), tissue plasminogen activator antigen (t-PA), fibrinogen, Factor VII and Factor VIII/von Willebrand factor antigen. Fasting lipid profiles, blood pressure and HOMA insulin sensitivity (%S) were also measured in siblings and in matched subjects without family history of diabetes. RESULTS: Hyperglycaemic and normoglycaemic siblings (7 female, 6 male) were aged, mean (SD) 56.8 (8.7) and 55.8 (8.4) years. Hyperglycaemic siblings had increased PAI-1 antigen, geometric mean (i.q.r.): 26.3 (15.1-45.6) vs 11.1 (2.1-23.3) ng/ml, p=0.0002, similar t-PA antigen, mean (SD) 9.5 (4.3) vs 7.4 (2.5) ng/ml, p=0.2 and fibrinogen 2.2 (0.3) vs 2.3 (0.6) g/l, p=0.5, and reduced %S 66.3 (30.5) vs 82.9 (25), p=0.04. PAI-1 correlated negatively with %S (r=-0.55, p=0.005). No significant differences were found in blood pressure or fasting lipids. CONCLUSION/INTERPRETATION: A minor increase in plasma glucose in non-diabetic sibling pairs of Type II (non-insulin-dependent) diabetic patients was associated with reduced insulin sensitivity, increased central adiposity and a doubling of PAI-1 antigen concentration, suggesting impaired fibrinolysis. It is possible that this could contribute to increased cardiovascular risk in these subjects. SN - 0012-186X UR - https://www.unboundmedicine.com/medline/citation/12107743/Hyperglycaemic_siblings_of_Type_II__non_insulin_dependent__diabetic_patients_have_increased_PAI_1_central_obesity_and_insulin_resistance_compared_with_their_paired_normoglycaemic_sibling_ L2 - https://doi.org/10.1007/s00125-002-0795-8 DB - PRIME DP - Unbound Medicine ER -