Different Patterns of Insulin Resistance in Relatives of Type 1 Diabetic Patients With Retinopathy or Nephropathy

The Genesis France-Belgium Study

  1. Samy Hadjadj, MD, PHD12,
  2. Franck Péan, PHD2,
  3. Yves Gallois, PHD3,
  4. Philippe Passa, MD4,
  5. Robert Aubert, PHD2,
  6. Laurent Weekers, MD5,
  7. Vincent Rigalleau, MD, PHD6,
  8. Bernard Bauduceau, MD7,
  9. Amine Bekherraz, MD8,
  10. Ronan Roussel, MD, PHD28,
  11. Bernard Dussol, MD9,
  12. Michel Rodier, MD10,
  13. Richard Marechaud, MD1,
  14. Pierre J. Lefebvre, MD, PHD5,
  15. Michel Marre, MD, PHD28 and
  16. for the Genesis France-Belgium Study *
  1. 1Department of Endocrinology and Diabetology, University Hospital, Poitiers, France
  2. 2Laboratoire de Nutrition Humaine, Faculté de Médecine X Bichat, Paris, France
  3. 3Department of Biochimie, Faculté de Médecine d’Angers, Angers, France
  4. 4Department of Endocrinology and Diabetology, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
  5. 5Diabetes Division, Nutrition and Metabolic Disorders, Department of Medicine, Centre Hospitalier Universitaire Sart Tilman, Liege, Belgium
  6. 6Department of Nutrition and Diabetology, Centre Hospitalier Universitaire Groupe Sud, Pessac, France
  7. 7Department of Diabetology, Begin Military Hospital, Saint Mandé, France
  8. 8Department of Endocrinology, Diabetology and Nutrition, Bichat Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France
  9. 9Department of Nephrology, Sainte Marguerite Hospital, Marseille, France
  10. 10Department of Endocrinology, University Hospital, Nimes, France
  1. Address correspondence and reprint requests to Michel Marre, Department of Endocrinology, DiabetologyNutrition, Bichat Hospital, Assistance Publique des Hôpitaux de Paris, 46 rue Henri Huchard, 75877 Paris Cedex 18, France. E-mail: michel.marre{at}bch.ap-hop-paris.fr

Abstract

OBJECTIVE—Insulin resistance may be a risk factor for diabetic microangiopathy, which may have a familial component. We carried out a family-based study to determine which components of the insulin resistance syndrome are associated with diabetic retinopathy and nephropathy in type 1 diabetes.

RESEARCH DESIGN AND METHODS—The Genesis France-Belgium Study is a multicenter binational study designed to investigate the genetic factors involved in the microvascular complications of type 1 diabetes using a family-based design. Probands were type 1 diabetic patients with diabetic retinopathy (classified as background, preproliferative, or proliferative) and possibly diabetic nephropathy (absent, incipient, established, or advanced). The insulin resistance score of their first-degree relatives was calculated according to their BMI and history of arterial hypertension, lipid disorders, and type 2 diabetes.

RESULTS—The insulin resistance score of relatives was positively correlated with the albumin excretion rate (P = 0.0009) and fasting plasma glucose (P = 0.0003) and HbA1c (P < 0.0001) concentrations. This score was higher in the relatives of probands with than in those without diabetic nephropathy (P = 0.0370). Similarly, it was higher in relatives of subjects with proliferative diabetic retinopathy than in those of probands without, even after controlling for subjects with versus without diabetic nephropathy (P = 0.0379). However, the components of the insulin resistance score in relatives differed according to the severity of diabetic retinopathy or nephropathy in the probands. Obesity and history of arterial hypertension were most common in relatives of probands with proliferative diabetic retinopathy, whereas obesity and history of lipid disorders were most common in the relatives of probands with diabetic nephropathy.

CONCLUSIONS—Familial insulin resistance segregates with diabetic complications: lipid disorders and obesity segregate with diabetic nephropathy, whereas arterial hypertension and obesity segregate with diabetic retinopathy.

Footnotes

  • *

    ↵* A complete list of Genesis France-Belgium Study members can be found in the appendix.

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted August 10, 2004.
    • Received January 14, 2004.
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  1. doi: 10.2337/diacare.27.11.2661 Diabetes Care November 2004 vol. 27 no. 11 2661-2668
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