From "thrifty genotype" to "hefty fetal phenotype": The relationship between high birthweight and diabetes in Saskatchewan registered Indians

Background: Intrauterine factors have been implicated in the pathogenesis o f Type 2 diabetes mellitus (T2DM). Methods: In a 1:1 matched pairs case-control study, high and low birthweigh t (HBW, LBW rates in Saskatchewan Registered Indian (RI) diabetic cases wer e compared with corresponding rates in RI without diabetes, and non-RI peop le with and without diabetes. Results: Birthweights were available for 73% of the 1,366 cases and 3 x 1,3 66 controls. A greater proportion of RI diabetics were born with HBW (> 400 0 grams) compared to RI non-diabetics (16.2% vs 10.7%; p <0.01). There was a significant association between HBW (but not LBW [< 2500 grams]) and diab etes for RI people (OR 1.63 [95% Cl 1.20, 2.241), which was stronger for RI females and strengthened progressively from mid to late 20th century. Interpretation: Certain causes of HBW may predispose to subsequent developm ent of T2DM in Canadian Aboriginal people ("hefty fetal phenotype" ["hefty fetal type"] hypothesis). Programs that optimize healthy pregnancies could reduce T2DM incidence in future generations.