title: Characterization of metabolically unhealthy normal-weight individuals: Risk factors and their associations with type 2 diabetes.
abstract: OBJECTIVE
  A proportion of type 2 diabetes cases arise from normal-weight individuals who can therefore be considered to be "metabolically unhealthy normal-weight" (MUH-NW). It remains unclear which factors account for this access risk. Our aims were to identify risk factors for type 2 diabetes in normal-weight individuals and to compare the strengths of their associations with type 2 diabetes to that observed in overweight and obese participants.
  
  
  METHODS
  A case-cohort, including 2027 sub-cohort participants and 706 incident type 2 cases, was designed within the population-based European Prospective Investigation into Cancer and Nutrition Potsdam study. Adjusted means and relative frequencies of anthropometric, lifestyle and biochemical risk factors were calculated in groups stratified by BMI and incident diabetes status. Cox regressions were applied to evaluate associations between these variables and diabetes risk stratified by BMI category.
  
  
  RESULTS
  MUH-NW individuals were characterized by known diabetes risk factors, e.g. they were significantly more likely to be male, former smokers, hypertensive, and less physically active compared to normal-weight individuals without incident diabetes. Higher waist circumference (women: 75.5 vs. 73.1cm; men: 88.0 vs. 85.1cm), higher HbA1c (6.1 vs. 5.3%), higher triglycerides (1.47 vs. 1.11 mmol/l), and higher levels of high sensitive C-reactive protein (0.81 vs. 0.51 mg/l) as well as lower levels of HDL-cholesterol (1.28 vs. 1.49 mmol/l) and adiponectin (6.32 vs. 8.25 μg/ml) characterized this phenotype. Stronger associations with diabetes among normal-weight participants compared to overweight and obese (p for interaction<0.05) were observed for height, waist circumference, former smoking, and hypertension.
  
  
  CONCLUSIONS
  Normal-weight individuals who develop diabetes have higher levels of diabetes risk factors, however, frequently still among the normal range. Still, hypertension, elevated HbA1c and lifestyle risk factors might be useful indicators of risk.
authors: Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Germany.
authors: Nathalie
authors: N
authors: Eckel
authors: Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Germany.
authors: Kristin
authors: K
authors: Mühlenbruch
authors: Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors: Karina
authors: K
authors: Meidtner
authors: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors: Heiner
authors: H
authors: Boeing
authors: German Center for Diabetes Research (DZD), Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center München at the University of Tübingen, Tübingen, Germany; Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany.
authors: Norbert
authors: N
authors: Stefan
authors: Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Germany. Electronic address: mschulze@dife.de.
authors: Matthias B
authors: MB
authors: Schulze
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001835:Body Weight; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006973:Hypertension / Q000150:complications; D008019:Life Style; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D055105:Waist Circumference
chemical_list: D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D008055:Lipids; C517652:hemoglobin A1c protein, human
keywords: Anthropometry; Biomarkers; Metabolically unhealthy normal-weight; Risk factors; Type 2 diabetes